JP2012140449A - Noxious organism control agent - Google Patents

Abstract

A pest control agent comprising a specific pyridine derivative is provided.
A pyridine derivative represented by the following formula:

[In the formula, Ar ^′ represents an optionally substituted pyridyl group or an optionally substituted pyrimidyl group; R ₁ represents a hydrogen atom or the like; Y represents a hydrogen atom, a halogen atom, a hydroxyl group, a halogen atom; R _4e represents an alkyl group _optionally substituted by, an alkyloxy group optionally substituted by a halogen atom, a cyano group, a formyl group, or a nitro group, and R _4e represents an alkyl group substituted by a halogen. However, when Ar ^′ represents a 6-chloro-3-pyridyl group, R ₁ represents a hydrogen atom, Y represents a 5-methyl group, and R _4e does not represent a trifluoromethyl group.]
[Selection figure] None

Description

  The present invention relates to a novel amine derivative and a pest control agent using the same.

  Many pest control agents have been found so far, but new drugs are still required due to problems such as a decrease in drug sensitivity, long-lasting effects, and safety during use.

  In particular, in paddy rice cultivation in East Asia and Southeast Asia, as shown in Non-Patent Document 1, neonicotinoids represented by imidacloprid, and main insecticides including phenylpyrazoles represented by fipronil, etc. As a result, the damage caused by the planthoppers that have developed drug resistance has become apparent, and there is a expectation of a specific medicine for the planthoppers that have developed resistance.

  Regarding the amine derivative having a heterocyclic ring, Patent Document 1 describes a monoalkylamine compound having a cyano group on the nitrogen atom, and its insecticidal activity against aphids, but the specific disclosure of the dialkylamine compound is not disclosed. There is no description about the control activity against pests other than aphids.

  Patent Document 2 describes an amine derivative having a 2,6-dichloro-4-pyridyl group and having a carboxyl group on the nitrogen atom, and its bactericidal and insecticidal activities. The ring is not disclosed.

  Non-Patent Document 2 and Non-Patent Document 3 disclose amine derivatives having a 6-chloro-3-pyridyl group and an acetyl group on the nitrogen atom as metabolites or reaction intermediates. Its pest control activity is not described. Non-Patent Document 4 discloses an amine derivative having a 6-chloro-3-pyridyl group and having an N-methylcarbamoyl group and an N-formylcarbamoyl group on the nitrogen atom. Is not described.

  Patent Document 3 discloses a plurality of compounds having the same ring structure as the compound represented by the formula (Ie), but its use is a herbicide and there is no description about pest control.

  Patent Document 4 discloses the structural formula of N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide. However, the production method thereof is not disclosed at all, and is not included in the list of compound groups in which pest control activity is recognized (No. 3 of Patent Document 4). Table 2, Table 3).

  Patent Document 5 discloses the structural formula of N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide. However, the production method thereof is not disclosed at all (Example 7 of Table 7 of Patent Document 5), and is not listed as an example of a compound having pest control activity in the Examples.

  Non-Patent Document 5 discloses a plurality of compounds having a ring structure similar to the compound represented by the formula (Ie) described later, but is merely disclosed as a synthetic intermediate.

  Patent Document 6 discloses a plurality of compounds having a ring structure similar to the compound represented by formula (Ie), but does not disclose or suggest a compound having a trifluoroacetic acid imino structure.

JP 2003-26661 A International Publication No. 2002/050035 European publication 432600 JP 5-78323 European Publication No.268915 European Publication No. 259738

Pest Management Science (2008), 64 (11), 1115-1121 Journal of Agricultural and Food Chemistry, 2010, 58 (4), 2419 Pest Management Science, 2005, 61 (8), 742 Journal of Photochemistry and Photobiology B: Biology 2010, 98 (1), 57 Chemische Berichte (1955), 88, 1103-8

  It is an object of the present invention to provide a novel pest control agent to solve the problems of existing drugs such as reduced drug sensitivity, sustained effect and safety during use in the pest control field. And

  One of the important problems in the present invention is that it has an excellent control effect on the green planthopper, white-spotted planthopper, and brown planthopper, which have become important pests in the field of rice in recent years. It is intended to provide a drug that exhibits high activity and that can be used safely by reducing the opportunity for workers to be exposed to the drug during soil treatment, seed treatment, seedling box treatment, and the like.

  As a result of intensive studies to solve the above problems, the present inventors have found that the amine derivative represented by the chemical formula (I) has an excellent activity as a pest control agent.

  That is, according to the present invention, the following inventions are provided.

  (1) A pest control agent comprising at least one compound represented by the following chemical formula (I) and a salt thereof.

[In the formula, Ar represents an optionally substituted phenyl group, or an optionally substituted 5- to 6-membered heterocycle;
R1 represents a hydrogen atom or a C1-6 alkyl group
R2 is a C1-6 alkylcarbonyl group in which the alkyl part may be substituted with a halogen atom, a C1-6 alkyloxycarbonyl group in which the alkyl part may be substituted with a halogen atom, and the alkyl part is substituted with a halogen atom. An optionally substituted C1-6 alkylsulfonyl group, CONR6R7, a C1-6 O, O′-alkylphosphoryl group in which the alkyl moiety may be substituted with a halogen atom, a cyano group, a formyl group or a nitro group;
R3 is a C1-8 alkylene group optionally substituted by a halogen atom, a C2-8 alkenylene group optionally substituted by a halogen atom, a C2-8 alkynylene group optionally substituted by a halogen atom, or a substituted group. An optionally substituted phenylene group, or an optionally substituted 5- to 6-membered heterocyclic divalent group,
R4 represents a hydrogen atom, a cyano group, an optionally substituted phenyl group, an optionally substituted 3-8 membered cyclic alkyl group, an optionally substituted 3-8 membered heterocycle, a halogen atom, OR5, OCOR5, OCOOR5, COR5, COOR5, SR5, SOR5, SO ₂ R5, N-CO-OR8, N-CO-SR8, N-CS-OR8, N-CS-SR8, NO-CO-R8, O- CO-R8, O-CO-OR8, O-CO-SR8, O-CS-OR8, O-CS-SR8, S-CS-OR8, S-CS-SR8, S-CO-OR8, S-CO- SR8, S-CS-R8, or NR9R10, O-CO-NR9R10, O-CS-NR9R10, S-CO-NR9R10, or S-CS-NR9R10, where R5 is optionally substituted by a halogen atom C1 -6 alkyl group, an aryl group which may be substituted with a halogen atom, and an aralkyl group which may be substituted with a halogen atom.

  R6 and R7 each independently represent a C1-6 alkyl group which may be substituted with a hydrogen atom or a halogen atom.

  R8 represents an optionally substituted C1-6 alkyl group, and the optionally substituted substituent is a halogen atom, a C1-4 alkyloxycarbonyl group, a C1-4 alkylcarbonyl group, a halogen atom or a halogen atom. A benzoyl group, a C1-4 alkyloxy group, or a C1-4 alkylthio group which may be substituted with a C1-4 alkyl group which may be substituted by

  R9 and R10 are each independently a hydrogen atom, a formyl group, a C1-6 alkyl group optionally substituted with a halogen, a C1-6 alkylcarbonyl group optionally substituted with a halogen atom, or an alkyl moiety. Is an optionally substituted C1-6 alkylcarbonyloxy group, an optionally substituted phenyl group (as an optionally substituted substituent, a halogen atom or a halogen atom may be substituted) C1-4 alkyl group, C1-4 alkyloxy group which may be substituted with a halogen atom), benzyl group which may be substituted (optionally substituted substituents are substituted with halogen or halogen An optionally substituted C1-4 alkyl group, a C1-4 alkyloxy group optionally substituted by halogen), or R9 and R10 form a ring to form one or more nitrogen Or shows a 3-10 membered heterocycloalkyl group containing an atom, or N, R9, R10 represents an aromatic heterocyclic ring 5-6 membered containing one or more nitrogen atoms to form a ring.

  N, R2, R3, and R4 may be taken together to represent a group represented by the formula (E).

Y represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-6 alkyl group which may be substituted with a halogen atom, a C1-6 alkyloxy group which may be substituted with a halogen atom, a cyano group, a formyl group, a nitro group R4e represents a C1-6 alkyl group substituted by halogen or a C1-6 alkyloxy group optionally substituted by halogen.

However, when Ar represents a 2,6-dichloro-4-pyridyl group, R2 does not represent a C1-6 alkyloxycarbonyl group in which the alkyl moiety may be substituted with a halogen atom.
(2) The pest control agent according to (1), wherein Ar in chemical formula (I) is a 6-chloro-3-pyridyl group or a 5-chloro-3-thiazolyl group.

  (3) R2 in the chemical formula (I) is a C1-6 alkylcarbonyl group in which the alkyl part may be substituted with a halogen atom, a C1-6 alkylsulfonyl group in which the alkyl part may be substituted with a halogen atom, or cyano The pest control agent according to (1) or (2), which is a group.

  (4) The pest control agent according to (1), wherein the compound represented by the chemical formula (I) is a compound represented by the following chemical formula (Ie).

  (5) The pest control agent according to (4), wherein R4e in chemical formula (Ie) is a C1-6 alkyl group substituted by a halogen atom.

  (6) The pest control agent according to (4), wherein Y in chemical formula (Ie) is a hydrogen atom or a halogen atom.

  (7) The pest control agent according to (4), wherein R4e in chemical formula (Ie) is a C1-6 alkyl group substituted by a halogen atom, and Y is a hydrogen atom or a halogen atom.

  (8) The compound represented by the chemical formula (Ie) is N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroaceta N- [1-((6-chloro-5-fluoropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1- ((6-Fluoropyridin-3-yl) methyl) pyridin-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1-((6-bromopyridin-3-yl) Methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1- (1- (6-chloropyridin-3-yl) ethyl) pyridine-2 (1H)- Ylidene] -2,2,2-trifluoroacetamide, -[1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide, 2-chloro-N- [1-((6-chloro Pyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide N- [1-((2-chloropyrimidin-5-yl) methyl) pyridine-2 (1H) -Ylidene] -2,2,2-trifluoroacetamide and N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,3,3 The pest control agent according to (4), which is a compound selected from the group consisting of 1,3-pentafluoropropanamide.

  (9) At least one insect species selected from the group consisting of lepidopterous insects, semilepidopterous insects, thrips insect pests, diptera insects, coleoptera insects, animal parasitic fleas and mites, and dog filamentous insects The pest control agent according to any one of (1) to (8), which has a control activity against.

  (10) The pest control agent according to any one of (1) to (9), wherein the pest is an agricultural or horticultural pest or an animal parasitic pest.

  (11) The pest control agent according to any one of (1) to (9), wherein the pest is a drug-resistant pest.

  (12) An amine derivative represented by the following chemical formula (I) or a salt thereof.

[In the formula, Ar represents an optionally substituted phenyl group, or an optionally substituted 5- to 6-membered heterocycle;
R1 represents a hydrogen atom or a C1-6 alkyl group
R2 is a C1-6 alkylcarbonyl group in which the alkyl part may be substituted with a halogen atom, a C1-6 alkyloxycarbonyl group in which the alkyl part may be substituted with a halogen atom, and the alkyl part is substituted with a halogen atom. An optionally substituted C1-6 alkylsulfonyl group, CONR6R7, a C1-6 O, O′-alkylphosphoryl group in which the alkyl moiety may be substituted with a halogen atom, a cyano group, a formyl group or a nitro group;
R3 is a C1-8 alkylene group optionally substituted by a halogen atom, a C2-8 alkenylene group optionally substituted by a halogen atom, a C2-8 alkynylene group optionally substituted by a halogen atom, or a substituted group. An optionally substituted phenylene group, or an optionally substituted 5- to 6-membered heterocyclic divalent group,
R4 represents a hydrogen atom, a cyano group, an optionally substituted phenyl group, an optionally substituted 3-8 membered cyclic alkyl group, an optionally substituted 3-8 membered heterocycle, a halogen atom, OR5, OCOR5, OCOOR5, COR5, COOR5, SR5, SOR5, SO ₂ R5, N-CO-OR8, N-CO-SR8, N-CS-OR8, N-CS-SR8, NO-CO-R8, O- CO-R8, O-CO-OR8, O-CO-SR8, O-CS-OR8, O-CS-SR8, S-CS-OR8, S-CS-SR8, S-CO-OR8, S-CO- SR8, S-CS-R8, or NR9R10, O-CO-NR9R10, O-CS-NR9R10, S-CO-NR9R10, or S-CS-NR9R10, where R5 is optionally substituted by a halogen atom C1 -6 alkyl group, an aryl group which may be substituted with a halogen atom, and an aralkyl group which may be substituted with a halogen atom.

  R6 and R7 each independently represent a C1-6 alkyl group which may be substituted with a hydrogen atom or a halogen atom.

  R8 represents an optionally substituted C1-6 alkyl group, and the optionally substituted substituent is a halogen atom, a C1-4 alkyloxycarbonyl group, a C1-4 alkylcarbonyl group, a halogen atom or a halogen atom. A benzoyl group, a C1-4 alkyloxy group, or a C1-4 alkylthio group which may be substituted with a C1-4 alkyl group which may be substituted by

  R9 and R10 are each independently a hydrogen atom, a formyl group, a C1-6 alkyl group optionally substituted by a halogen atom, a C1-6 alkylcarbonyl group optionally substituted by a halogen atom, an alkyl A C1-6 alkylcarbonyloxy group in which the moiety may be substituted by a halogen atom, an optionally substituted phenyl group (the optionally substituted substituent may be a halogen atom or a halogen atom, A good C1-4 alkyl group, an optionally substituted C1-4 alkyloxy group), an optionally substituted benzyl group (optionally substituted substituents include halogen or halogen substituted) An optionally substituted C1-4 alkyl group, or a halogenated C1-4 alkyloxy group), or one or more of R9 and R10 form a ring Or shows a 3-10 membered heterocycloalkyl group containing a nitrogen atom, or N, R9, R10 represents an aromatic heterocyclic ring 5-6 membered containing one or more nitrogen atoms to form a ring.

  In addition, when Ar represents an optionally substituted pyridyl group or an optionally substituted pyrimidyl group, N, R2, R3, and R4 together may represent a group represented by the formula (E) .

  Y is a hydrogen atom, a halogen atom, a hydroxyl group, a C1-6 alkyl group which may be substituted with a halogen, a C1-6 alkyloxy group which may be substituted with a halogen atom, a cyano group, a formyl group, or a nitro group. R4e represents a C1-6 alkyl group substituted by a halogen atom or a C1-6 alkyloxy group optionally substituted by a halogen atom.

However, when Ar represents a 2,6-dichloro-4-pyridyl group, R2 does not represent a C1-6 alkyloxycarbonyl group in which the alkyl moiety may be substituted with a halogen atom, and Ar represents 6-chloro-3 -When R 1 represents a pyridyl group, R 1 represents a hydrogen atom, Y represents a 5-methyl group, and R 4e does not represent CF 3]
(13) The amine derivative or salt thereof according to (12), wherein Ar in chemical formula (I) is a 6-chloro-3-pyridyl group or a 5-chloro-3-thiazolyl group.

  (14) R2 in the chemical formula (I) is a C1-6 alkylcarbonyl group in which the alkyl portion may be substituted with a halogen atom, a C1-6 alkylsulfonyl group in which the alkyl portion may be substituted with a halogen atom, or The amine derivative or salt thereof according to (12) or (13), which is a cyano group.

  (15) The amine derivative or a salt thereof according to (12), wherein the compound represented by the chemical formula (I) is a compound represented by the following chemical formula (Ie ′).

  Here, Ar ′ represents an optionally substituted pyridyl group, an optionally substituted pyrimidyl group, Y represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-6 alkyl group optionally substituted by a halogen atom, C1-6 alkyloxy group optionally substituted by a halogen atom, cyano group, formyl group, nitro group, R4e represents a C1-6 alkyl group substituted by halogen, or C1-6 optionally substituted by halogen 6 represents an alkyloxy group.

However, when Ar ′ represents a 6-chloro-3-pyridyl group, R1 represents a hydrogen atom, Y represents a 5-methyl group, and R4e does not represent a trifluoromethyl group.]
(16) The amine derivative or salt thereof according to (15), wherein R 4e in chemical formula (Ie ′) is a C 1-6 alkyl group substituted with a halogen atom.

  (17) The amine derivative or the salt thereof according to (15), wherein Y in the chemical formula (Ie ′) is a hydrogen atom or a halogen atom.

  (18) The amine derivative or the salt thereof according to (15), wherein R 4e in chemical formula (Ie ′) is a C 1-6 alkyl group substituted by a halogen atom, and Y is a hydrogen atom or a halogen atom.

  (19) The compound represented by the above formula (Ie ′) is N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoro. Loacetamide, N- [1-((6-chloro-5-fluoropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [ 1-((6-Fluoropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1-((6-bromopyridin-3- Yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1- (1- (6-chloropyridin-3-yl) ethyl) pyridine-2 (1H ) -Ilidene] -2,2,2-trifluoroacetami N- [1-((6-chloropyridin-3-yl) methyl) pyridin-2 (1H) -ylidene] -2,2-difluoroacetamide, 2-chloro-N- [1-((6- Chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide, N- [1-((2-chloropyrimidin-5-yl) methyl) pyridine-2 (1H ) -Ylidene] -2,2,2-trifluoroacetamide and N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,3,3,3 -The amine derivative or its salt as described in (15) which is a compound selected from the group consisting of pentafluoropropanamide.

  (20) At least one insect species selected from the group consisting of lepidopterous insects, semilepidopterous insects, thrips insect pests, diptera insects, coleoptera insects, animal parasitic fleas and mites, and dog filamentous insects The amine derivative or the salt thereof according to any one of (12) to (19), which has a controlling activity against.

  (21) A method for controlling pests using the pest control agent according to any one of (1) to (9) or the amine derivative or salt thereof according to any one of (12) to (20).

  (22) The pest control agent according to any one of (1) to (9), or the amine derivative or salt thereof according to any one of (12) to (20), plant seeds, roots, tubers, Agro-horticultural pests comprising treating a bulb, rhizome, soil, nutrient solution in hydroponic culture, solid medium in hydroponic culture, or a carrier for growing the plant to permeate the compound into the plant Control method.

  (23) The method according to (21), wherein the pest is an agricultural or horticultural pest or an animal parasitic pest.

  (24) The method of claim 21, wherein the pest is a drug resistant pest.

  By using the amine derivative of the present invention, it is possible to effectively control the long-tailed beetle, the Japanese cutworm, the aphids, the planthoppers, the leafhoppers, the thrips and many other pests.

N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide crystal powder prepared by the first production method It is a graph which shows the result of a X-ray crystal analysis. Differential crystals of N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide prepared by the first production method It is a graph which shows the result of a scanning calorimetric analysis. N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide crystal powder prepared by the second production method It is a graph which shows the result of a X-ray crystal analysis. Differential crystals of N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide prepared by the second production method It is a graph which shows the result of a scanning calorimetric analysis. Differential crystals of N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide prepared by the third production method It is a graph which shows the result of a scanning calorimetric analysis. N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide crystal powder prepared by the fourth production method It is a graph which shows the result of a X-ray crystal analysis. Differential crystal of N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide prepared by the fourth production method It is a graph which shows the result of a scanning calorimetric analysis. Difference in crystals of N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide prepared by the fifth production method It is a graph which shows the result of a scanning calorimetric analysis.

  In the amine derivative represented by the chemical formula (I), which is an active ingredient of the pesticidal agent provided by the present invention, Ar is an optionally substituted phenyl group, or an optionally substituted 5 to 6 membered member. It represents a heterocycle, preferably a 5- to 6-membered heterocycle which may be substituted.

  Examples of the substituent which may be substituted include a halogen atom, a C1-4 alkyl group which may be substituted with a halogen atom, an alkyloxy group which may be substituted with a halogen atom, a hydroxyl group, a cyano group, a nitro group, etc. And preferably a halogen atom or a C1-4 alkyl group optionally substituted by a halogen atom.

  Specific examples of the optionally substituted phenyl group include phenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 3-cyanophenyl group, 4-cyanophenyl group, 3-nitrophenyl group, 4-nitrophenyl group. 3,5-dichlorophenyl group, 4-methylphenyl group, 4-methoxyphenyl group, 3,5-dibromophenyl group, 2,4-dibromophenyl group, 4-fluorophenyl group, 4-bromophenyl group, 3- Examples thereof include a nitro-5-bromophenyl group and a 3,5-bistrifluoromethylphenyl group, and a 4-nitrophenyl group, a 4-cyanophenyl group, and a 3,5-dibromophenyl group are preferable.

  Specific examples of the optionally substituted 5- to 6-membered heterocycle include pyridine, thiazole, tetrahydrofuran, furan and the like, preferably a 3-pyridyl group and a 3-thiazolyl group, more preferably 6 -Chloro-3-pyridyl group, 5-chloro-3-thiazolyl group, 6-chloro-5-fluoro-3-pyridyl group, 6-bromo-3-pyridyl group, 6-fluoro-3-pyridyl group, 5, 6-dichloro-3-pyridyl group, 6-trifluoromethyl-3-pyridyl group, particularly preferably 6-chloro-3-pyridyl group, 6-fluoro-3-pyridyl group, 6-chloro-5-fluoro 3-pyridyl group and 6-bromo-3-pyridyl group.

  In the chemical formula (I), “C1-6 alkyl group” represented by R1 is a chain, branched, cyclic, or a combination thereof having 1 to 6 carbon atoms. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more. Specific examples include a methyl group, an ethyl group, a propyl group, an isopropyl group, and a cyclopropyl group, and a methyl group and an ethyl group are preferable.

  R2 is a C1-6 alkylcarbonyl group in which the alkyl part may be substituted with a halogen atom, a C1-6 alkyloxycarbonyl group in which the alkyl part may be substituted with a halogen atom, and the alkyl part is substituted with a halogen atom. C1-6 alkylsulfonyl group, CONR6R7, optionally substituted by a halogen atom, C1-6 O, O′-alkylphosphoryl group, cyano group, formyl group or nitro group, preferably A C1-6 alkylcarbonyl group in which the alkyl moiety may be substituted with a halogen atom, a C1-6 alkylsulfonyl group in which the alkyl moiety may be substituted with a halogen atom, and a cyano group.

  R3 is a C1-8 alkylene group optionally substituted by a halogen atom, a C2-8 alkenylene group optionally substituted by a halogen atom, a C2-8 alkynylene group optionally substituted by a halogen atom, or a substituted group. An optionally substituted phenylene group and an optionally substituted 5- to 6-membered heterocyclic divalent group, preferably a C1-8 alkylene group optionally substituted by a halogen atom.

R4 represents a hydrogen atom, a cyano group, an optionally substituted phenyl group, an optionally substituted 3-8 membered cyclic alkyl group, an optionally substituted 3-8 membered heterocycle, a halogen atom, OR5, OCOR5, OCOOR5, COR5, COOR5, SR5, SOR5, SO ₂ R5, N-CO-OR8, N-CO-SR8, N-CS-OR8, N-CS-SR8, NO-CO-R8, O- CO-R8, O-CO-OR8, O-CO-SR8, O-CS-OR8, O-CS-SR8, S-CS-OR8, S-CS-SR8, S-CO-OR8, S-CO- SR8, S-CS-R8, or NR9R10, O-CO-NR9R10, O-CS-NR9R10, S-CO-NR9R10, S-CS-NR9R10 are shown.

  R5 represents a C1-6 alkyl group which may be substituted with a halogen atom, an aryl group which may be substituted with a halogen atom, or an aralkyl group which may be substituted with a halogen atom.

  R6 and R7 each independently represent a C1-6 alkyl group which may be substituted with a hydrogen atom or a halogen atom.

  R8 represents an optionally substituted C1-6 alkyl group, and the optionally substituted substituent is a halogen atom, a C1-4 alkyloxycarbonyl group, a C1-4 alkylcarbonyl group, a halogen atom or a halogen atom. A benzoyl group, a C1-4 alkyloxy group, or a C1-4 alkylthio group which may be substituted with a C1-4 alkyl group which may be substituted by

  R9 and R10 are each independently a hydrogen atom, a formyl group, a C1-6 alkyl group optionally substituted by a halogen atom, a C1-6 alkylcarbonyl group optionally substituted by a halogen atom, an alkyl A C1-6 alkylcarbonyloxy group in which the moiety may be substituted by a halogen atom, an optionally substituted phenyl group (the optionally substituted substituent may be a halogen atom or a halogen atom, A good C1-4 alkyl group, an optionally substituted C1-4 alkyloxy group), an optionally substituted benzyl group (optionally substituted substituents include halogen or halogen substituted) An optionally substituted C1-4 alkyl group, or a halogenated C1-4 alkyloxy group), or one or more of R9 and R10 form a ring Or shows a 3-10 membered heterocycloalkyl group containing a nitrogen atom, or N, R9, R10 represents an aromatic heterocyclic ring 5-6 membered containing one or more nitrogen atoms to form a ring.

  `` C1-6 alkyl group optionally substituted by a halogen atom '' represented by R5, R6, R7, R8, R9, and R10 is a chain, branched, cyclic, or a combination thereof having 1 to 6 carbon atoms The upper limit of the number of halogen atoms that are alkyl groups and may be substituted is the number of hydrogen atoms that the alkyl group has. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more.

  Specific examples of the “C1-6 alkyl group optionally substituted with a halogen atom” represented by R5 include a methyl group, an ethyl group, an n-propyl group, a difluoromethyl group, a trifluoromethyl group, a chloromethyl group, A 2-trifluoroethyl group is mentioned.

  Specific examples of the “C1-6 alkyl group optionally substituted by a halogen atom” represented by R6 and R7 include a methyl group, an ethyl group, an n-propyl group, a difluoromethyl group, a trifluoromethyl group, and chloromethyl. Group, 2-trifluoroethyl group.

As the “C1-6 alkyl group optionally substituted by a halogen atom” represented by R8, specifically, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an n-pentyl group, A 2-trifluoroethyl group and a 2-chloroethyl group are exemplified, and a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, and an n-pentyl group are preferable.
Specific examples of the “C1-6 alkyl group optionally substituted by a halogen atom” represented by R9 and R10 include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, and an n-pentyl group. Group, 2-trifluoroethyl group, and 2-chloroethyl group are preferable, and methyl group and ethyl group are preferable.

  "C1-6 alkylcarbonyl group in which the alkyl moiety may be substituted with a halogen atom" represented by R2, R9 and R10; "C1-6 alkyloxycarbonyl in which the alkyl moiety may be substituted with a halogen atom" represented by R2 Group "," C1-6 alkylsulfonyl group in which the alkyl moiety may be substituted with a halogen atom "," C1-6 O, O'-alkylphosphoryl group in which the alkyl moiety may be substituted with a halogen atom ", The alkyl moiety in the “C1-6 alkylcarbonyloxy group in which the alkyl moiety may be substituted with a halogen atom” represented by R9 and R10 has 1 to 6 carbon atoms, and is linear, branched, cyclic, or their An alkyl group represented by a combination. The upper limit of the number of halogen atoms that may be substituted is the number of hydrogen atoms that the alkyl group has. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more.

  The “C1-6 alkylcarbonyl group in which the alkyl moiety may be substituted with a halogen atom” represented by R2 specifically includes an acetyl group, an ethylcarbonyl group, an n-propylcarbonyl group, a difluoroacetyl group, a trifluoroacetyl group. Group, pentafluoroacetyl group, chloroacetyl group, trichloroacetyl group, and trifluoroacetyl group is preferable.

  The “C1-6 alkyloxycarbonyl group in which the alkyl moiety may be substituted with a halogen atom” represented by R2 specifically includes a methyloxycarbonyl group, an ethyloxycarbonyl group, an n-propyloxycarbonyl group, chloromethyl Examples thereof include an oxycarbonyl group and a 2-trifluoroethyloxycarbonyl group.

  The “C1-6 alkylsulfonyl group in which the alkyl moiety may be substituted with a halogen atom” represented by R2 specifically includes a methylsulfonyl group, an ethylsulfonyl group, an n-propylsulfonyl group, a difluoromethylsulfonyl group, Examples thereof include a fluoromethylsulfonyl group, a trichloromethylsulfonyl group, and a 2-trifluoromethylsulfonyl group, and a trifluoromethylsulfonyl group is preferable.

  The “C1-6 O, O′-alkylphosphoryl group in which the alkyl moiety may be substituted with a halogen atom” represented by R2 is specifically O, O′-dimethylphosphoryl group, O, O′-diethyl. A phosphoryl group is mentioned.

  Specific examples of the “C1-6 alkylcarbonyl group in which the alkyl moiety may be substituted by a halogen atom” represented by R5 include an acetyl group, an ethylcarbonyl group, an n-propylcarbonyl group, an isopropylcarbonyl group, 2-chloro An ethylcarbonyl group is mentioned.

  Specific examples of the “C1-6 alkylcarbonyl group in which the alkyl moiety may be substituted with a halogen atom” represented by R9 and R10 are methyloxycarbonyl group, ethyloxycarbonyl group, n-propyloxycarbonyl group, isopropyl Examples thereof include an oxycarbonyl group and a 2-chloroethyloxycarbonyl group.

  R9 and R10 represent an “C1-6 alkylcarbonyloxy group in which the alkyl moiety may be substituted with a halogen atom”, specifically, a methylcarbonyloxy group, an ethylcarbonyloxy group, an n-propylcarbonyloxy group, Examples include isopropylcarbonyloxy group and 2-chloroethylcarbonyloxy group.

  The “C1-8 alkylene group optionally substituted by a halogen atom” represented by R3 is a C1-C8 alkylene group represented by a straight chain, branched, cyclic, or a combination thereof, and is substituted. The upper limit of the number of halogen atoms that may be used is the number of hydrogen atoms of the alkyl group. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more. Specific examples include methylene group, ethylene group, propylene group, butylene group, fluoromethylene group, 1-chloroethylene group, 2-methylethylene group, cyclopropylene group, 2-cyclopropylethylene group, 1,3- A cyclopentylene group etc. are mentioned, Preferably they are a methylene group, ethylene group, and a propylene group, More preferably, it is an ethylene group.

  The `` C2-8 alkenylene group optionally substituted by a halogen atom '' represented by R3 is a C2-C8 alkenylene group represented by a linear, branched, cyclic or combination thereof, and is substituted. The upper limit of the number of halogen atoms that may be used is the number of hydrogen atoms of the alkyl group. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more. Specific examples include vinylene group, 1-propenylene group, 2-fluoro-1-propenylene group, 2-methyl-1-propenylene group, and 2-cyclohexene-1,4-ylene group.

  The `` C2-8 alkynylene group optionally substituted by a halogen atom '' represented by R3 is an alkynylene group having 2 to 8 carbon atoms represented by a linear, branched, cyclic or combination thereof, and is substituted. The upper limit of the number of halogen atoms that may be used is the number of hydrogen atoms of the alkyl group. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more. Specific examples include propynylene group and butynylene group, preferably 1-propynylene.

  The “optionally substituted phenylene” represented by R3 is a divalent group excluding two hydrogen atoms of benzene, and examples of the substituent include a halogen atom and a C1-optionally substituted halogen atom. 4Alkyl group, alkyloxy group optionally substituted by a halogen atom, hydroxyl group, cyano group, nitro group and the like can be mentioned. Specific examples include a phenylene group, a 4-fluorophenylene group, and a 2-methylphenylene group.

  The “optionally substituted 5- to 6-membered heterocyclic divalent group” represented by R3 is a divalent group excluding two hydrogen atoms of the 5- to 6-membered heterocyclic ring. , A halogen atom, a C1-4 alkyl group which may be substituted with a halogen atom, an alkyloxy group which may be substituted with a halogen atom, a hydroxyl group, a cyano group, a nitro group, and the like. A specific example is a 2-pyridinylene group.

  Examples of the substituent that may be substituted by the “optionally substituted pyridyl group” or “optionally substituted pyrimidyl group” represented by Ar ′ of the compound represented by the formula (Ie ′) include a halogen atom, halogen Examples thereof include a C1-4 alkyl group which may be substituted with an atom, an alkyloxy group which may be substituted with a halogen atom, a hydroxyl group, a cyano group, a nitro group, and the like, preferably a halogen atom.

  Preferred embodiments of Ar of the compound represented by the formula (Ie) and Ar ′ of the compound represented by the formula (Ie ′) include 3-pyridyl group, 6-chloro-3-pyridyl group, 5-chloro-3-thiazolyl Group, 6-chloro-5-fluoro-3-pyridyl group, 6-bromo-3-pyridyl group, 6-fluoro-3-pyridyl group, 5,6-dichloro-3-pyridyl group, 6-trifluoromethyl- 3-pyridyl group, 2-chloro-5-pyrimidyl group, more preferably 6-chloro-3-pyridyl group, 6-fluoro-3-pyridyl group, 6-chloro-5-fluoro-3-pyridyl group, 6-bromo-3-pyridyl group and 2-chloro-5-pyrimidyl group.

  Y in the compounds represented by the formula (Ie) and the formula (Ie ′) represents 1 to 3 substituents which may be the same or different.

  The “C1-6 alkyl group optionally substituted by a halogen atom” represented by Y of the compounds represented by the formula (Ie) and the formula (Ie ′) is a chain, branched, cyclic, or a combination thereof. The upper limit of the number of halogen atoms that are alkyl groups of 1 to 6 and may be substituted is the number of hydrogen atoms that the alkyl group has. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more.

  Specific examples include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a t-butyl group, a trifluoromethyl group, and a 2-chloroethyl group, and a methyl group is preferable.

  Specific examples of the “C1-6 alkyloxy group optionally substituted with halogen” represented by Y include a methoxy group, an ethoxy group, a trifluoromethyl group, and a difluoromethyl group.

  A preferred embodiment of Y is a hydrogen atom or halogen, more preferably a hydrogen atom.

  The “C1-6 alkyl group substituted by a halogen atom” represented by R4e of the compounds represented by the formula (Ie) and the formula (Ie ′) is a chain, branched, cyclic, or a combination thereof having 1 to 6 is an alkyl group, and the upper limit of the number of substituted halogen atoms is the number of hydrogen atoms of the alkyl group. When it contains a branched or cyclic alkyl group, it is clear that the carbon number is 3 or more.

  Specifically, trifluoromethyl group, trichloromethyl group, difluorochloromethyl group, difluoromethyl group, dichloromethyl group, dibromomethyl group, chloromethyl group, difluoroethyl group, dichloroethyl group, 2,2,2-trifluoro And an ethyl group, a pentafluoroethyl group, a difluorocyclopropyl group, etc., preferably a trifluoromethyl group, a trichloromethyl group, a dichloromethyl group, a difluoromethyl group, a difluorochloromethyl group, a chloromethyl group, and a pentafluoroethyl group. More preferably a trifluoromethyl group, a difluoromethyl group, a difluorochloromethyl group, a chloromethyl group or a pentafluoroethyl group.

  Specific examples of the “C1-6 alkyloxy group optionally substituted by halogen” represented by R4e include a methoxy group, an ethoxy group, an isopropyloxy group, a trifluoromethoxy group, and the like.

  A preferred embodiment of R4e is a C1-6 alkyl group optionally substituted by halogen, more preferably a trifluoromethyl group, a difluoromethyl group, a difluorochloromethyl group, a chloromethyl group, or a pentafluoroethyl group. .

  Examples of the salt of the amine derivative represented by the chemical formula (I), which is an active ingredient of the pest control agent provided by the present invention, are acid addition salts that are acceptable in agricultural and veterinary medicine, such as hydrochloride, nitrate, sulfuric acid. Examples thereof include salts, phosphates and acetates.

In a preferred embodiment of the compound represented by formula (I),
Ar is 4-nitrophenyl group, 4-cyanophenyl group, 3,5-dibromophenyl group, 2,4-dibromophenyl group, 6-chloro-3-pyridyl group, 5-chloro-3-thiazolyl group, 6 -Chloro-5-fluoro-3-pyridyl group, 6-bromo-3-pyridyl group, 6-fluoro-3-pyridyl group, 5,6-dichloro-3-pyridyl group, or 6-trifluoromethyl-3- Represents a pyridyl group,
R1 represents a hydrogen atom or a methyl group,
R2 represents a C1-6 alkylcarbonyl group in which the alkyl part may be substituted with a halogen atom, a C1-6 alkylsulfonyl group in which the alkyl part may be substituted with a halogen atom, or a cyano group,
R3 represents a methylene group, an ethylene group, a propylene group, or a 1-propynylene group,
R4 represents a hydrogen atom, a cyano group, SR5 (R5 represents a C1-6 alkyl group which may be substituted with halogen), S-CS-OR8, S-CS-SR8 (R8 is substituted with halogen) An optionally substituted C1-6 alkyl group).

  Examples of preferred compounds are the following compounds (i) to (iii).

(I) Ar is 4-cyanophenyl group, 4-nitrophenyl group, 3,5-dichlorophenyl group, 3,5-dibromophenyl group, 2,4-dibromophenyl group, 4-bromophenyl group, 3-nitro -5-bromophenyl group, 6-chloro-3-pyridyl group, 5-chloro-3-thiazolyl group, 6-chloro-5-fluoro-3-pyridyl group, 6-trifluoromethyl-3-pyridyl group ,
R1 represents a hydrogen atom,
R2 represents a trifluoromethylsulfonyl group,
R3 represents a methylene group, an ethylene group, or a 1-propynylene group,
R4 is a compound showing a hydrogen atom or a cyano group,
(Ii) Ar represents a 6-chloro-3-pyridyl group, a 5-chloro-3-thiazolyl group, or a 6-trifluoromethyl-3-pyridyl group;
R1 represents a hydrogen atom or a methyl group,
R2 represents a cyano group or a trifluoromethylcarbonyl group,
R3 represents an ethylene group,
R4 is a hydrogen atom, SR5 (R5 represents a C1-6 alkyl group which may be substituted with halogen), S-CS-OR8, S-CS-SR8 (R8 may be substituted with halogen) A compound showing a good C1-6 alkyl group),
(Iii) Compound represented by formula (Ie) Examples of particularly preferred compounds are the following compounds (i) to (iii).

(I) Ar is 4-cyanophenyl group, 4-nitrophenyl group, 3,5-dichlorophenyl group, 3,5-dibromophenyl group, 2,4-dibromophenyl group, 4-bromophenyl group, 3-nitro -5-bromophenyl group, 6-chloro-3-pyridyl group, 5-chloro-3-thiazolyl group, 6-chloro-5-fluoro-3-pyridyl group, 6-trifluoromethyl-3-pyridyl group ,
R1 represents a hydrogen atom,
R2 represents a trifluoromethylsulfonyl group,
R3 represents a methylene group, an ethylene group, or a 1-propynylene group,
R4 is a compound showing a hydrogen atom,
(Ii) Ar represents a 6-chloro-3-pyridyl group, a 5-chloro-3-thiazolyl group, or a 6-trifluoromethyl-3-pyridyl group;
R1 represents a hydrogen atom or a methyl group,
R2 represents a cyano group or a trifluoromethylcarbonyl group,
R3 represents an ethylene group,
R4 is SR5 (R5 represents a C1-6 alkyl group optionally substituted with halogen), S-CS-OR8, S-CS-SR8 (R8 is C1 optionally substituted with halogen) A compound showing 6 alkyl group),
(Iii) Compound represented by formula (Ie) A preferred embodiment of the compound represented by formula (Ie) is:
Ar is 3-pyridyl group, 6-chloro-3-pyridyl group, 5-chloro-3-thiazolyl group, 6-chloro-5-fluoro-3-pyridyl group, 6-bromo-3-pyridyl group, 6- Fluoro-3-pyridyl group, 5,6-dichloro-3-pyridyl group, 6-trifluoromethyl-3-pyridyl group, 2-chloro-5-pyrimidyl group,
R1 represents a hydrogen atom, a methyl group or an ethyl group,
Y represents a hydrogen atom, a halogen atom, or a methyl group,
R4e is a compound showing a trifluoromethyl group, trichloromethyl group, dichloromethyl group, difluoromethyl group, difluorochloromethyl group, chloromethyl group, pentafluoroethyl group,
More preferably
Ar is 6-chloro-3-pyridyl group, 6-fluoro-3-pyridyl group, 6-chloro-5-fluoro-3-pyridyl group, 6-bromo-3-pyridyl group, 2-chloro-5-pyrimidyl group Group,
R1 represents a hydrogen atom or a methyl group,
Y represents a hydrogen atom
R4e is a compound showing a trifluoromethyl group, a difluoromethyl group, a difluorochloromethyl group, a chloromethyl group, or a pentafluoroethyl group.

  The compound represented by the chemical formula (I) as an active ingredient of the pest control agent of the present invention is preferably 500 ppm for foliage treatment, 0.1 mg / seedling soil irrigation treatment, 2 μg / head topical application treatment, 50 ppm chemical solution It has a control activity (for example, death rate or morbidity rate of 30% or more, 50% or more, 80% or more, 100%) by immersion treatment in 200ppm and dry film treatment of 200ppm (test example of the present invention) checking). Further, it has a controlling activity (insecticidal effect) by 20 μg / plant seedling root treatment shown in Test Example 15 or motility evaluation under the culture condition of about 3 ppm shown in Test Example 21.

  In foliage treatment, more preferably, it has a controlling activity at a concentration of less than 500 ppm (for example, 400 ppm, 300 ppm, 200 ppm, 100 ppm, 50 ppm, 30 ppm, 10 ppm, 5 ppm, 3 ppm, 1.5 ppm, 1.25 ppm, 1 ppm, 0.5 ppm). Is.

  More preferably, the soil irrigation treatment has a controlling activity at a concentration of less than 0.1 mg / seedling (for example, 0.05 mg / seedling, 0.01 mg / seedling, 0.005 mg / seedling, 0.002 mg / seedling).

  More preferably, the topical application treatment has a controlling activity at a concentration of less than 2 μg / head (for example, 1 μg / head, 0.5 μg / head, 0.2 μg / head).

  In the dry film treatment, more preferably, it has a controlling activity at a concentration of less than 200 ppm (for example, 100 ppm, 50 ppm, 30 ppm, 10 ppm).

  In the soaking treatment, more preferably less than 20 μg / seedling (for example, 10 μg / seedling, 5 μg / seedling, 2 μg / seedling, 1 μg / seedling, 0.5 μg / seedling, 0.1 μg / seedling, 0.05 μg / seedling, 0.03 μg / Seedling, 0.01 μg / seedling) concentration.

  Specific examples of the compounds of the present invention are listed in Tables 1 to 5.

The most preferred compound is Compound No. 212: N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2 listed in Table 5 below. -Trifluoroacetamide,
Compound No. 227: N- [1-((6-chloro-5-fluoropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide,
Compound No. 229: N- [1-((6-fluoropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide,
Compound No. 231: N- [1-((6-bromopyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide,
Compound No. 237: N- [1- (1- (6-chloropyridin-3-yl) ethyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide,
Compound No. 238: N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide,
Compound No. 239: 2-chloro-N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide Compound No. 242: N- [ 1-((6-Chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,3,3,3-pentafluoropropanamide compound number 243: N- [1-((2- Chloropyrimidin-5-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide.

In addition, Compound No. 212 described in Table 5: N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide The physical properties are as follows. Nothing showing this physical property is described in any prior literature.
(A) In powder X-ray diffraction, it has a diffraction angle peak at least at the following diffraction angle (2θ).
Diffraction angles: 8.6 ± 0.2 °, 14.2 ± 0.2 °, 17.5 ± 0.2 °, 18.3 ± 0.2 °, 19.7 ± 0.2 °, 22.3 ± 0.2 °, 30.9 ± 0.2 °, 35.3 ± 0.2 °
(B) Melting | fusing point shows 155-158 degreeC in a differential scanning calorimetry (DSC).

  Examples of the insect species in which the pest control agent containing at least one compound of the present invention represented by the chemical formula (I) exhibits a controlling effect are as follows.

  Agricultural and horticultural pests include lepidopterous pests (for example, Lotus spider, Coleoptera, Acacia, Aomushi, Konaga, Shirochimogiyoto, Nikameiga, Kofomomeiga, Futabikogaga, Clamidae, Sinkiga, Clamidae, Agrotis sp.) Pests (Helicoverpa spp), Heliothis spp, etc., Hemiptera pests (eg, peach aphids, cotton aphids, Aphisfabae, corn aphids, pea aphids, potato aphids, bean aphids, tulip beetles) , Macrosiphum avenae, Methopolophium dirhodum, wheat beetle aphid, barley beetle, radish aphid, fake aphid, snowy aphid, Rosy apple aphid, phosphorus Aphids (Aphididae, Adelgidae, Phy11oxeridae) such as cotton beetles, Komikan Aphids, Citrus aphids, leafhoppers such as the leafhopper leafhoppers, Chanomidorihimebokoba, leafworms such as leafhoppers, leafhoppers, leafworms Stink bugs such as blue stink bugs, red bearded beetle, silver leaf whitefly, whitefly whitefly, whitefly whitefly (A1eyrodidae), stag beetle, citrus scale gar ida e , Ortheziidae, Ac1erdiae, Dacty1opiidae, Kerridae, Pseudococcidae, Coccidae, Eriococcidae, Asterolecaniidae, Beesonidae, Lecanodiaspididae, Cerococcidae), pods Eye pests (eg, rice weevil, azuki bean weevil, brown rice weevil, western corn root worm, southern corn root worm, sand squirrel, slatted beetle, killer whale beetle, cucumber potato beetle, Colorado potato potato beetle, mite beetle, worm beetle) For example, urticae, kanzawa spider mites, citrus spider mites, etc.), Hymenoptera pests (e.g., wasps), straight moth pests (e.g., grasshoppers), Diptera pests (e.g., houseflies, leafhoppers), thrips pests (e.g., And the like, and plant parasitic nematodes (for example, root-knot nematode, negusaresenchu, rice-singing nematode, pinewood nematode, etc.).

  Animal parasitic pests include ticks (eg, Lone star ticks, Gulf ticks, Rock ticks, Rocky forest ticks, West coast ticks, American dog ticks, Ticks, Ticks, Ticks, Ticks, Ticks, Ticks, Westerns Black mite, shulze mite, sheep mite, black mite, oyster mite, mite mite), tsume mites (e.g., cat ticks, mites), mites (e.g., mites, mites), mites (e.g. Hymenid mites (for example, ox-shocked mites, Inomimi mites), Saury mites (for example, avian mites), Spiders, Mites (for example, chickens) Sea urchins, spider mites), tsutsugamushi (e.g. Miyamatsu pine tsutsugamushi, red tsutsugamushi), fleas (e.g., cat fleas, human fleas, keops mud mines, murines), lice (e.g., dog lice, chicken lice), lice (E.g., pig lice, dog lice, body lice, human lice, white lice, bed bugs), house flies, cow flies, cow flies, horse flies, fly flies (e.g. Aedes aegypti), cuttlefish (e.g., Culex), anopheles, nuciferous, flyfish, sand turtle, house turtle, nematode (e.g., nematode, worm, roundworm) (e.g. Rodents), ciliate nematodes, metamorphosis (eg Swine lungworm, Cantonese schistosomiasis, cat lungworm), helminths, caecal worms (eg, chicken roundworm), roundworms (eg, Anisakis nematode, pig roundworm, horse roundworm, dog roundworm, cat roundworm), Rotating nematodes (e.g., bursula, spiny-mouthed jawworm, cat stomachworm, horoscope stomachworm, large-mouth horse stomachworm, chicken stomachworm, medinae), filamentous worms (e.g. Lymphoid filamentous worms, rotiferous filamentous worms, loar filamentous worms), nephroids, trichinella (eg, Trichuris elegans, Trichinella)), flukes (eg, Schistosoma japonicum, liver fluke), bald worms , And crustaceans (for example, suspicious leaves (for example, Manson striatum), circles (for example, Coleoptera)), protozoa, and the like.

  Sanitary pests, unpleasant pests, stored grain pests, stored food pests, and house pests include mosquitoes (for example, Aedes albopictus, Culex), cockroaches (for example, black-legged cockroaches, Japanese cockroaches, German cockroaches), coniferous mites (for example, mites) , Flies (for example, houseflies, nymphae, butterflies, drosophila, chironomids), flyfish, phylums, hymenoptera insects (for example, ant species such as the crocodile and fire ant, bees such as the giant hornet) Arthropods (for example, Paramecium, Funabushi, Dangamushi), Hemiptera insects (for example, bed bugs), polypods of arthropods (for example, centipedes, gejis, millipedes), arachnid arthropods Animals (eg, sea lions), Coleoptera insects (eg, beetles), terrestrial arthropods (eg, Insects (for example, giant beetles), grasshoppers (for example, caterpillars), coleopterous (for example, azuki beetle, weevil), kokunusuto, kokunosutomodoki, leopard beetle, beetle , Black butterfly insects (for example, moths, moths), scallops, termite insects (for example, termites, American white termites, taiwan termites), worms (for example, Yamatoshimi) and the like.

  Among these, preferred species of insects to which the pest control agent of the present invention is applied are lepidopterous insects, hemiptera pests, thrips pests, diptera pests, Coleoptera pests, animal parasitic fleas , Mites, dog filamentous worms (e.g. diamondback moth, scallops, cotton aphids, peach aphids, scallops, leafhoppers, white-spotted plant, leafhoppers, red-spotted winged turtles, red-winged beetles, tickling moths, tickling, And at least one insect species selected from the group consisting of dog filamentous insects), more preferably hemipods, Coleoptera, ticks, particularly preferably planthoppers and leafhoppers.

  Accordingly, the pest control agents provided by the present invention include, for example, agricultural and horticultural insecticides, animal endoparasite control agents, animal ectoparasite control agents, sanitary pest control agents, unpleasant pest control agents, grain storage and storage Food pest control agents, house pest control agents and the like can be mentioned, and preferred are agricultural and horticultural insecticides, animal endoparasite control agents, and animal ectoparasite control agents.

  The pest control agent of the present invention can be prepared using a carrier according to the method of use in addition to the compound represented by the chemical formula (I).

  When the pest control agent of the present invention is an agricultural pest control agent, it is usually mixed with an appropriate solid carrier, liquid carrier, gaseous carrier, surfactant, dispersing agent or other formulation auxiliary agent to prepare an emulsion or liquid. , Suspensions, wettable powders, flowables, powders, granules, tablets, oils, aerosols, smokes and the like.

  Examples of the solid carrier include talc, bennite, clay, kaolin, diatomaceous earth, vermiculite, white carbon, calcium carbonate and the like.

  Examples of the liquid carrier include alcohols such as methanol, n-hexanol and ethylene glycol, ketones such as acetone, methyl ethyl ketone and cyclohexanone, aliphatic hydrocarbons such as n-hexane, kerosene and kerosene, toluene, xylene and methylnaphthalene. Aromatic hydrocarbons such as diethyl ether, dioxane, tetrahydrofuran, etc., esters such as ethyl acetate, nitriles such as acetonitrile and isobutyronitrile, acid amides such as dimethylformamide and dimethylacetamide, soybean oil , Vegetable oils such as cottonseed oil, dimethyl sulfoxide, water and the like.

  Examples of the gaseous carrier include LPG, air, nitrogen, carbon dioxide gas, dimethyl ether and the like.

  Surfactants and dispersants for emulsification, dispersion, spreading, etc. include, for example, alkyl sulfates, alkyl (aryl) sulfonates, polyoxyalkylene alkyl (aryl) ethers, polyhydric alcohol esters, A lignin sulfonate can be used.

  Moreover, as an adjuvant for improving the property of a formulation, carboxymethylcellulose, gum arabic, polyethylene glycol, calcium stearate etc. can be used, for example.

  The above carriers, surfactants, dispersants, and adjuvants can be used alone or in combination as required.

  The content of the active ingredient in the preparation is not particularly limited, but is usually 1 to 75% by weight for an emulsion, 0.3 to 25% by weight for a powder, 1 to 90% by weight for a wettable powder, and 0.5 to 10 for a granule. % By weight.

The compound represented by the chemical formula (I), a preparation containing these, and a mixture of these with other pest control agents are harmful insects, plants, plant propagation materials (eg, seeds, plant foliage) Part, root, germinated plant, and young plant), soil, nutrient solution in hydroponic culture, solid medium in hydroponic culture, and rooms that need to prevent the invasion of pests it can. Applied plants include genetically modified crops.
These applications can be made before and after pest infestation.

  In particular, the compound represented by the chemical formula (Ie), a preparation containing these, and a mixture of them with other pest control agents, effective amounts, plant seeds, roots, tubers, bulbs, rhizomes, germinated Pests can be controlled by applying to an object selected from the group consisting of plants, seedlings, soil, nutrient solution in hydroponic culture, and solid medium in hydroponic culture, and osmotically transferred into the plant.

  When the application target is plant seeds, roots, tubers, bulbs or rhizomes, suitable examples of application methods are not particularly limited as long as they do not impede osmotic transfer, but immersion methods, powder coating methods, smearing methods , Spraying method, pellet method, coating method and the like.

  In the case of seeds, application methods include, for example, a dipping method, a powder coating method, a smearing method, a spraying method, a pellet method, a film method, and a fumigation method. The dipping method is a method in which seeds are immersed in a liquid drug solution. The powder coating method includes a dry powder coating method in which a powdered drug is attached to dry seeds, and a seed lightly soaked in water. There is a wet powder coating method to attach the drug in the shape. In addition, there are a smearing method in which a suspended drug is applied to the seed surface in a mixer and a spraying method in which the suspension is sprayed onto the seed surface. In addition, when pelletizing seeds with a filler into a certain size and shape, the pellet method in which the filler is mixed with the chemical, the coating method in which the seed is coated with a film containing the chemical, and in a sealed container A fumigation method that disinfects seeds with gasified chemicals can be mentioned.

  When applied to germinated plants and seedlings, these plants can be protected by application after sprouting, emergence from soil, and before transplantation by whole or part treatment by immersion. .

  In addition, when applied to seeds, roots, tubers, bulbs, rhizomes, etc., plant or immerse the seeds, roots, tubers, bulbs, rhizomes, etc. for a time sufficient for the drug to penetrate into the plant. Also mentioned. In this case, the immersion time and temperature are appropriately determined by those skilled in the art according to the application target, the type and amount of the drug, and the like. And although it does not specifically limit as penetration transfer time, For example, it is 1 hour or more. Moreover, as temperature in osmosis | permeation transfer, it is 5-45 degreeC, for example.

  As an application method to soil, for example, a preparation containing these compounds of the present invention and a granule of a mixture of them with other pest control agents are applied in or on the soil. Preferred soil application methods are spraying, strips, grooves, and planting hole application methods. Here, the spraying treatment includes surface treatment over the entire area to be treated and subsequent mechanical introduction into the soil.

  In addition, it is also an advantageous soil application method to apply by irrigating the soil with a solution obtained by emulsifying or dissolving a preparation containing these compounds of the present invention and a mixture of these and other pest control agents in water. .

  When applied to nutrient solutions in hydroponic culture systems such as hydroponics and sand culture, NFT (Nutrient Film Technique), rock medium cultivation, etc. for the production of vegetables and flowers It is also clear that the present compounds can be directly applied to the preparation containing these compounds and the mixture of these and other pest control agents to an artificial soil containing vermiculite and a solid medium containing an artificial mat for raising seedlings. .

  In the above application step, the effective amount of the compound of formula (I) or a salt thereof or the compound of formula (Ie) or a salt thereof is the same as that of the compound of formula (1) or formula (Ie) in the subsequent osmotic transfer step. An amount sufficient to penetrate into the plant is preferable.

  The effective amount can be appropriately determined in consideration of the nature of the compound, the type and amount of the object to be applied, the length of the subsequent osmotic transfer step, temperature, etc. For example, in the case of seeds, the formula (I) The amount of the compound or salt thereof or the compound of formula (Ie) or salt thereof is preferably 1 g to 10 kg, more preferably 10 g to 1 kg per 10 kg of seed. When applied to soil, the amount of the compound of formula (I) or a salt thereof or the compound of formula (Ie) or a salt thereof is preferably 0.1 g to 10 kg, more preferably 1 g to 1kg. When treating the foliage of a plant, the amount of the compound of formula (I) or a salt thereof or the compound of formula (Ie) or a salt thereof is preferably 0.1 to 10 kg, more preferably 1 g per 10 ares of cultivated land. It is desirable to process ~ 1kg.

  When the pest control agent of the present invention is an animal parasitic pest control agent, it is a liquid, emulsion, liquefied drop, spray, foam preparation, tablet, granule, fine granule, powder, capsule, tablet, It is provided as a chewable agent, injection agent, suppository, cream agent, shampoo agent, rinse agent, resin agent, smoke agent, poison bait, etc., but it is particularly preferable that it is provided as a liquid agent or a liquefied drop agent.

  The liquid preparation can further contain formulation emulsifiers such as ordinary emulsifiers, dispersants, spreading agents, wetting agents, suspending agents, preservatives, propellants, etc. A forming agent can also be blended. Surfactants for emulsification, dispersion, spreading, etc. include, for example, soaps, polyoxyalkylene alkyl (aryl) ethers, polyoxyethylene alkyl allyl ethers, polyoxyethylene fatty acid esters, higher alcohols, alkylaryls A sulfonate or the like can be used. Examples of the dispersant include casein, gelatin, polysaccharides, lignin derivatives, saccharides, and synthetic water-soluble polymers. Examples of spreading / wetting agents include glycerin and polyethylene glycol. Examples of the suspending agent include casein, gelatin, hydroxypropyl cellulose, and gum arabic. Examples of the stabilizing agent include phenolic antioxidants (BHT, BHA, etc.) and amine antioxidants (diphenylamine, etc.). ) And organic sulfur-based antioxidants. Examples of the preservative include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate. The above carriers, surfactants, dispersants, and adjuvants can be used alone or in combination as required. Furthermore, you may contain a fragrance | flavor, a synergist, etc. The content of the active ingredient in the pesticidal composition of the present invention is usually 1 to 75% by weight in a liquid preparation.

  Examples of the carrier used for preparing the cream include non-volatile hydrocarbons (such as liquid paraffin), lanolin-added oils and fats, higher fatty acids, fatty acid esters, animal and vegetable oils, silicone oils, and water. Furthermore, emulsifiers, moisturizers, antioxidants, fragrances, borax, and ultraviolet absorbers can be used alone or in combination as required. Examples of the emulsifier include fatty acid sorbitan, polyoxyethylene alkyl ether, and fatty acid polyoxyethylene. The content of the active ingredient in the pest control agent of the present invention is usually 0.5 to 70% by weight for creams.

  For capsules, pills or tablets, the active ingredient in the composition of the present invention is appropriately subdivided and mixed with a diluent or a carrier such as starch, lactose, talc, and a disintegrant such as magnesium stearate. And / or a binder can be added and used as a tablet if necessary.

  Injections must be prepared as sterile solutions. An injection may contain, for example, sufficient salt or glucose to make the solution isotonic with blood. Carriers that can be used to prepare injectables include glycerides, esters such as benzyl benzoate, isopropyl myristate and fatty acid derivatives of propylene glycol, organic solvents such as N-methylpyrrolidone, glycerol formal. The content of the active ingredient in the pest control agent of the present invention is usually 0.01 to 10% by weight for injections.

  Examples of the carrier for preparing the resin agent include vinyl chloride polymers and polyurethane. If necessary, plasticizers such as phthalates, adipic esters, and stearic acid can be added to these substrates. After kneading the active ingredient in the substrate, it can be molded by injection molding, extrusion molding, press molding or the like. Furthermore, it can be made into an animal ear tag or an animal insect repellent collar through appropriate steps such as molding, cutting and cutting.

  Carriers for poisonous baits include dietary substances and attractants (flours such as wheat flour and corn flour, starches such as corn starch and potato starch, sugars such as granulated sugar, maltose and honey, foods such as glycerin, onion flavor and milk flavor. And animal powders such as flavors, rice cake powders, and fish meals, and various pheromones). The content of the active ingredient of the pest control agent of the present invention is usually 0.0001 to 90% by weight for poison baits.

  Pests can be controlled by administering the pest control agent of the present invention into the body of an applied animal orally or by injection, or by administering to the whole or part of the body surface of the applied animal. Moreover, pests can also be controlled by covering the places where pests are expected to invade, parasitize and move with the pest control agent of the present invention.

  The pest control agent of the present invention may be used as it is, but depending on the case, it can be diluted with water, a liquid carrier, a commercially available shampoo, rinse, bait, a breeding house underlay or the like.

  In addition, the pest control agent according to the present invention can be used by mixing with other fungicides, insecticides, acaricides, herbicides, plant growth regulators, fertilizers and the like. Drugs that can be used in combination include those described in the Pesticide Manual (published by The British Crop Protection Council 13th edition) and Shibuya Index (published by SHIBUYA INDEX 13th edition, 2008, published by SHIBUYA INDEX RESEARCH GROUP). It is done. More specifically, as insecticides, acaricides or nematicides, acephate, dichlorvos, EPN, fenitrothion, fenamifos, prothiofos, profenofos , Organophosphate compounds such as pyraclofos, chlorpyrifos-methyl, diazinon, fosthiazate, imiciafos, mesomyl, thiodicarb, aldicarb ( Like aldicarb, oxamyl, propoxur, carbaryl, fenobucarb, ethiofencarb, fenothiocarb, pirimicarb, carbofuran, benfuracarb Carbamate compounds, cartap, nereistoxin derivatives such as thiocyclam, organochlorine compounds such as dicofol, tetradifon, permethrin, tefluthrin, cypermethrin pyrethroid compounds such as (cypermethrin), deltamethrin, cyhalothrin, fenvalerate, fluvalinate, etofenprox, silafluofen, diflubenzuron, teflubenzuron benzoylurea compounds such as teflubenzuron, flufenoxuron, chlorfluazuron, juvenile hormone-like compounds such as metoprene, and molting hormone-like compounds such as chromafenozide It is done. In addition, other compounds include buprofezin, hexythiazox, amitraz, chlordimeform, pyridaben, fenpyroxymate, pyrimidifen, tebufenrad, tebufenrad, tebufenrad, tebufenrad ), Fluacrypyrim, acequinocyl, cyflumetofen, flubendizmide, ethiprole, fipronil, etoxazole, imidaclopric, imidacloprid, imidacloprid, imidaclopridum thiamethoxam, acetamiprid, nitenpyram, thiacloprid, dinotefuran, pymetro Gin (pymetrozine), bifenazate (spirodiclofen), spiromesifen (spiromesifen), flonicamid (flonicamid), chlorfenapyr (chlorfenapyr), pyriproxyfen (pyriproxyfen), indoxacarb (indoxacarb), pyridalyl ( pyridalyl), spinosad, avermectin, avermectin, milbemycin, cyenopyrafen, spinetoram, pyrifluquinazon, chlorantraniliprole, cyantraniliprole, cyantraniliprole , Spirotetramat, lepimectin, metaflumizone, pyrafluprole, pyriprole, hydramethylnon, triazame Examples include triazamate, sulfoxaflor, flupyradifurone, flometoquin, organometallic compounds, dinitro compounds, organic sulfur compounds, urea compounds, triazine compounds, and hydrazine compounds. It is done.

  The pest control agent of the present invention can be used in combination or in combination with microbial pesticides such as BT agents and entomopathogenic virus agents.

  Examples of the bactericides used in combination or in combination include strobilurin such as azoxystrobin, kresoxym-methyl, trifloxystrobin, metinominostrobin, oryastrotrobin. Compounds, mepanipyrim, pyrimethanil, anilinopyrimidine compounds such as cyprodinil, triadimefon, bitertanol, triflumizole, metconconazole, metoconazole Propiconazole, penconazole, flusilazole, flusilazole, myclobutanil, cyproconazole, tebuconazole, hexaconazole, prochloraz, simecona azole compounds such as zole), quinoxaline compounds such as quinomethionate, dithiocarbamates such as maneb, zineb, mancozeb, polycarbamate, and propineb Compounds such as phenylcarbamate compounds such as diethofencarb, organochlorine compounds such as chlorothalonil, quintozene, benomyl, thiophanate-methyl, carbendazole Benzimidazole compounds, metalaxyl, oxadixyl, ofurase, benalaxyl, furalaxyl, phenylamide compounds such as cyprofuram, diclofluranide (dichlofluanid) Such as sulfenic acid system Copper hydroxide, copper-based compounds such as oxine-copper, isoxazole-based compounds such as hydroxyisoxazole, fosetyl-aluminium, torquelophos -Organophosphorus compounds such as tolclofos-methyl, captan, captafol, N-halogenothioalkyl compounds such as folpet, procymidone, iprodione Dicarboxyimide compounds such as vinchlozolin, flutolanil, mepronil, furamepyr, thifluzamide, boscalid, carboxyanilide compounds such as penthiopyrad Morphs such as fenpropimorph, dimethomorph Oline compounds, organotin compounds such as fenthin hydroxide, fenthin acetate, fludioxonil, cyanopyrrole compounds such as fenpiclonil, and other tricyclazoles ( tricyclazole), pyroquilon, carpropamid, diclocymet, phenoxanil, fthalide, fluazinam, fluazinam, cymoxanil, triforine, pyrifox, pyrifox Fenarimol, fenpropidin, pencicuron, ferimzone, cyazofamid, iprovalicarb, benthiavalicarb-isopropyl, iminoctadine albecyl salt (iminoctadin) -albesilate , Ciflufenamid (cyflufenamid), kasugamycin, validamycin, streptomycin, oxolinic-acid, tebufloquin, probenazole, and thiadinyl isothianil It is done.

[Synthesis of the Compound of the Present Invention]
(1) The compound represented by the following chemical formula (Ia) is:

[In the formula, Ar represents an optionally substituted phenyl group, or an optionally substituted 5- to 6-membered heterocycle;
R2 is a C1-6 alkylcarbonyl group in which the alkyl part may be substituted with a halogen atom, a C1-6 alkyloxycarbonyl group in which the alkyl part may be substituted with a halogen atom, and the alkyl part is substituted with a halogen atom. An optionally substituted C1-6 alkylsulfonyl group, CONR6R7 (wherein R6 and R7 are independently of each other a C1-6 alkyl group optionally substituted by a hydrogen atom or a halogen), the alkyl moiety is substituted by a halogen atom An optionally substituted C1-6 O, O'-alkylphosphoryl group, a cyano group, a formyl group or a nitro group;
R3 is a C1-8 alkylene group optionally substituted by a halogen atom, a C2-8 alkenylene group optionally substituted by a halogen atom, a C2-8 alkynylene group optionally substituted by a halogen atom, or a substituted group. An optionally substituted phenylene group, an optionally substituted 5- to 6-membered heterocyclic divalent group,
R4 represents a hydrogen atom, an optionally substituted phenyl group, an optionally substituted 3- to 8-membered carbon and heterocycle, a halogen atom, OR5, OCOR5, OCOOR5, COR5, COOR5, SR5, SOR5, SO ₂ R5 (wherein R5 represents a C1-C6 alkyl group, aryl group, aralkyl group optionally substituted by halogen), N-CO-OR8, N-CO-SR8, N-CS-OR8, N-CS -SR8, NO-CO-R8, O-CO-R8, O-CO-OR8, O-CO-SR8, O-CS-OR8, O-CS-SR8, S-CS-OR8, S-CS-SR8 , S-CO-OR8, S-CO-SR8 (wherein R8 represents an optionally substituted C1-6 alkyl group, the substituent is halogen, C1-4 alkyloxycarbonyl group, C1-4 alkyl A carbonyl group, a halogen or a benzoyl group optionally substituted by a C1-4 alkyl group optionally substituted by a halogen, a C1-4 alkyloxy group, a C1-4 alkylthio group), NR9R10 (where R9, R10 are independently of each other a hydrogen atom C1-6 alkyl group optionally substituted by halogen, C1-6 alkylcarbonyl group optionally substituted by halogen atom, C1-6 alkylcarbonyl optionally substituted by halogen atom Represents an oxy group).

However, when Ar represents a 2,6-dichloro-4-pyridyl group, R2 does not represent a C1-6 alkyloxycarbonyl group in which the alkyl moiety may be substituted with a halogen atom. ]
In the compound represented by the following chemical formula (II), a halide, anhydride, ester or the like of R2 [R2 has the same meaning as defined in the above chemical formula (I)] can be added in the presence or absence of a base. It can be obtained by reaction.

[In the formula, Ar, R3, and R4 have the same meaning as defined in chemical formula (I) above]
R2 halides, anhydrides, and esters include carboxylic acid halides, carboalkyloxyhalides, sulfonyl halides, O, O'-alkylphosphoryl halides, carboxylic anhydrides, dialkyl dicarbonates, carboxylic acid esters, and carbonates. Specifically, it is preferable to use acetyl chloride, ethyl chloroformate, methanesulfonyl chloride, diethyl chlorophosphate, trifluoroacetic anhydride, ethyl formate, and the like.

  When the reaction is performed in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, Tertiary amines such as triethylamine and unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be performed using no solvent or a solvent that does not affect the reaction. When using a solvent, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform, chlorobenzene, Halogen hydrocarbons such as dichlorobenzene and solvents such as water can be used alone or in combination, but dimethylformamide, acetonitrile, ethers, Rorometan, it is preferable to use such as chloroform.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  When R2 in the chemical formula (Ia) is a C1-6 alkylcarbonyl group in which the alkyl moiety may be substituted with a halogen atom, the compound represented by the chemical formula (II) may be converted to R2′-COOH [where R2 'Can also be obtained by reacting a carboxylic acid represented by a C1-6 alkyl group optionally substituted with a halogen atom in the presence of a dehydrating condensing agent.

  As the dehydrating condensing agent, carbodiimide compounds such as dicyclohexylcarbodiimide and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride can be used.

  The reaction is preferably performed using a solvent. For example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, ethyl acetate, butyl acetate Esters such as, aromatic hydrocarbons such as benzene, xylene and toluene, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, halogens such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene Hydrocarbons can be used alone or in combination of two or more, but dichloromethane, chloroform, etc. are preferably used.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  When R2 in the chemical formula (Ia) is a cyano group, the compound represented by the formula (II) can be obtained by reacting a known cyanating reagent in the presence or absence of a base.

  As the cyanating reagent, bromocyanide, iodocyanide, 1-cyanoimidazole, 1-cyanobenzotriazole, substituted or unsubstituted benzenesulfonylcyanide and the like can be used.

  When the reaction is performed in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal acetates such as sodium acetate, and tertiary amines such as triethylamine. Substituted or unsubstituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane , Aliphatic hydrocarbons such as heptane and octane, halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene, and one or more solvents such as water Possible, diethyl ether, ethers such as tetrahydrofuran, dichloromethane, it is preferable to use a halogenated hydrocarbon such as chloroform. The reaction can usually be carried out at 0 to 100 ° C., and it is preferable to add a cyanating reagent at 0 ° C. and slowly raise the temperature to about 20 to 50 ° C.

  The compound represented by the chemical formula (II) can be synthesized from the compound represented by the following chemical formula (IIIa) or (IIIb).

[Where X represents halogen or OTs, OMs, etc.]

[Ar in the formula has the same meaning as defined in chemical formula (I) above]
When synthesized from the compound represented by (IIIa), it can be obtained by reacting the compound represented by (IIIa) with the compound represented by the following chemical formula (IVa) in the presence or absence of a base. it can.

[Wherein R3 and R4 have the same meaning as defined in chemical formula (I) above]
When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane Solvents such as aliphatic hydrocarbons such as heptane and octane, and halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene can be used alone or in combination. That is, dimethylformamide, acetonitrile, ethers, dichloromethane, are preferably used such as chloroform.

  The reaction can usually be carried out at 0 to 200 ° C., and a reagent is added at 0 ° C., the temperature is slowly raised to 20 to 50 ° C., and the temperature is preferably raised to a higher temperature depending on the progress of the reaction.

  The amount of the compound represented by (IIIa) to the compound represented by (IVa) is preferably 1 mol or less with respect to 1 mol of the compound represented by (IVa).

  When synthesized from the compound represented by (IIIb), it can be obtained by reacting the compound represented by (IIIb) with the compound represented by the following chemical formula (IVb) in the presence or absence of a base. it can.

[Wherein R3 and R4 have the same meaning as defined in the above chemical formula (I), X represents a halogen atom or OTs, OMs, etc.]
When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, pyridines having unsubstituted or substituted groups such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane , Aliphatic hydrocarbons such as heptane and octane, halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene, and one or more solvents such as water Possible, dimethylformamide, acetonitrile, ethers, dichloromethane, are preferably used such as chloroform.

  The reaction can be usually carried out at 0 ° C. to 200 ° C. A reagent is added at 0 ° C., the temperature is slowly raised to 20-50 ° C., and the temperature is preferably raised to a higher temperature depending on the progress of the reaction.

  It is preferable that the addition amount of the compound represented by (IVb) with respect to the compound represented by (IIIb) is 1 mol or less with respect to 1 mol of the compound represented by (IIIb).

  In addition, the compound represented by (II) above forms an imine by adding a compound represented by the following chemical formula (IVc) to the compound represented by (IIIb) in the presence or absence of an acid. Thereafter, it can be obtained by carrying out a reduction reaction.

[Wherein R3 ′ and R3 ″ may be the same or different and each represents a hydrogen atom or a C1-7 alkyl group, and R3 ′ and R3 ″ may be combined to form a ring. However, R3 ′ and R3 ″ do not represent hydrogen atoms at the same time, and the sum of the number of carbon atoms of R3 ′ and R3 ″ is smaller than 7. R4 has the same meaning as defined in chemical formula (I) above]
In the reaction, a solvent is preferably used. As the solvent, lower alcohols such as methanol and ethanol, acetonitrile, dichloromethane, dichloroethane and the like can be used, but methanol, ethanol and the like are preferably used.

  In the case of using an acid, for example, hydrochloric acid, substituted, unsubstituted benzenesulfonic acid, acetic acid and the like can be used.

  The reduction reaction can be performed using a hydride reducing reagent such as sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride.

  Alternatively, the reduction reaction can also be performed by a catalytic hydrogenation reaction using a metal catalyst. As the metal catalyst, palladium, platinum, rhodium, nickel, iron or the like can be used.

  The reaction can usually be carried out at 20 to 100 ° C.

  (2) The compound represented by (Ia) can also be synthesized from a compound represented by the following chemical formula (Va).

[In the formula, Ar and R2 have the same meaning as defined in the above chemical formula (Ia)]
(Va) is reacted with X-R3R4 [R3R4 has the same meaning as defined in chemical formula (I) above, X represents a halogen atom] in the presence or absence of a base. Obtainable.

  When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Non-substituted or substituted pyridines such as tertiary amines such as pyridine and 4-dimethylaminopyridine can be used, but alkali metal hydrides such as sodium hydride are preferably used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane , Aliphatic hydrocarbons such as heptane and octane, halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene, and one or more solvents such as water Possible, dimethylformamide, acetonitrile, ethers, dichloromethane, are preferably used such as chloroform.

  The compound represented by (Va) is a compound represented by (IIIb), a halide, anhydride, ester, or the like of R2 [R2 has the same meaning as defined in the above chemical formula (I)] It can be obtained by reacting in the presence or absence.

  Examples of halides, anhydrides and esters of R2 include carboxylic acid halides, carboalkyloxy halides, sulfonyl halides, O, O′-alkylphosphoryl halides, carboxylic anhydrides, dialkyl dicarbonates, carboxylic acid esters, carbonate esters, cyanoesters. A halide or the like can be used.

  The reaction preferably uses a solvent, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethyl sulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate , Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform and chlorobenzene , Halogen hydrocarbons such as dichlorobenzene, and solvents such as water can be used alone or in combination of two or more. It is preferable to use Le acids.

  When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

Further, the compound represented by (Va) is a compound represented by (IIIa), a compound represented by R2-NH ₂ [R2 has the same meaning as defined in the above chemical formula (I)], It can also be obtained by reacting in the presence or absence of a base.

  The reaction preferably uses a solvent, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethyl sulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate , Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform and chlorobenzene One kind or a combination of two or more kinds of solvents such as halogen hydrocarbons such as dichlorobenzene and water can be used, and acetonitrile or the like is preferably used.

  When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  (3) The compound represented by (Ia) can also be synthesized from a compound represented by the following chemical formula (Vb).

[Wherein R2, R3 and R4 have the same meaning as defined in chemical formula (I) above]
A compound represented by (Vb) and a compound represented by Ar-CH2-X [Ar represents the same meaning as defined in the above chemical formula (I), X represents a halogen atom or OTs, OMs, etc.] Can be obtained by reacting in the presence or absence of a base.

  When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Although non-substituted or substituted pyridines such as tertiary amines such as pyridine and 4-dimethylaminopyridine can be used, alkali metal hydrides such as sodium hydride are preferably used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane , Aliphatic hydrocarbons such as heptane and octane, halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene, and one or more solvents such as water Possible, dimethylformamide, acetonitrile, ethers, dichloromethane, are preferably used such as chloroform.

  The compound represented by (Vb) is a compound represented by (IVa), a halide, anhydride, ester, or the like of R2 [R2 has the same meaning as defined in the above chemical formula (I)] It can be obtained by reacting in the presence or absence.

  Examples of halides, anhydrides and esters of R2 include carboxylic acid halides, carboalkyloxy halides, sulfonic acid halides, O, O′-alkylphosphoryl halides, carboxylic acid anhydrides, dialkyloxydicarbonates, carboxylic acid esters, carbonyls. Acid esters, cyanohalides and the like can be used.

  The reaction preferably uses a solvent, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethyl sulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate , Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform and chlorobenzene , Halogen hydrocarbons such as dichlorobenzene, and solvents such as water can be used alone or in combination of two or more. It is preferable to use Le acids.

  When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

In addition, the compound represented by (Vb) is represented by X-R3R4 [R3, R4 has the same meaning as defined in the above chemical formula (I), X represents a halogen atom], R2-NH ₂ [R2 is A compound represented by the same meaning as defined in the above chemical formula (I)] can also be obtained by reacting in the presence or absence of a base.

  The reaction preferably uses a solvent, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethyl sulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate , Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform and chlorobenzene , Halogen hydrocarbons such as dichlorobenzene, solvents such as water can be used alone or in combination of two or more, but acetonitrile, tetrahydrofuran, etc. are used Door is preferable.

  When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

(4) The compound represented by the following chemical formula (Ib) is a compound represented by R ₂ NH ₂ [R 2 is the same as defined in the above chemical formula (I)], ArCH ₂ X [X is a halogen atom Can be obtained by reacting in the presence or absence of a base.

[In the formula, Ar and R2 have the same meaning as defined in chemical formula (I) above]
When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, pyridines having unsubstituted or substituted groups such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane Solvents such as aliphatic hydrocarbons such as heptane and octane, and halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene can be used alone or in combination. That is, it is preferable to use such as acetonitrile.

  The reaction can usually be carried out at 0 to 200 ° C, and it is preferred to carry out the reaction at 60 to 80 ° C by adding a reagent at 20 to 40 ° C.

  (5) The compound represented by the following chemical formula (Ic) is:

[Where R1 represents a C1-6 alkyl group, and Ar, R2, R3, R4 have the same meaning as defined in the above chemical formula (I)]
In the compound represented by the following chemical formula (VIa), a halide, an anhydride, an ester, or the like of R2 [R2 has the same meaning as defined in the above chemical formula (I)] is present in the presence or absence of a base. It can obtain by making it react.

[Wherein R1 represents a C1-6 alkyl group, and Ar, R3, R4 have the same meaning as defined in the above chemical formula (I)]
R2 halides, anhydrides, and esters include carboxylic acid halides, carboalkyloxyhalides, sulfonyl halides, O, O'-alkylphosphoryl halides, carboxylic anhydrides, dialkyl dicarbonates, carboxylic acid esters, and carbonates. For example, acetyl chloride, ethyl chloroformate, methanesulfonyl chloride, diethyl chlorophosphate, trifluoroacetic anhydride, ethyl formate and the like are preferably used.

  When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane , Aliphatic hydrocarbons such as heptane and octane, halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene, and one or more solvents such as water Possible, dimethylformamide, acetonitrile, ethers, dichloromethane, are preferably used such as chloroform.

  The reaction can usually be carried out at −80 to 100 ° C., but preferably carried out in the range of 20 to 50 ° C.

  When R2 of the compound represented by (Ic) is a C1-6 alkylcarbonyl group in which the alkyl moiety may be substituted with a halogen atom, the compound represented by (VIa) is substituted with R2′-COOH [here R2 ′ can also be obtained by reacting a carboxylic acid represented by a C1-6 alkyl group optionally substituted with a halogen atom in the presence of a dehydrating condensing agent.

  As the dehydrating condensing agent, carbodiimide compounds such as dicyclohexylcarbodiimide and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride can be used.

  The reaction is preferably performed using a solvent. For example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, ethyl acetate, butyl acetate Esters such as, aromatic hydrocarbons such as benzene, xylene and toluene, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, halogens such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene Hydrocarbons can be used alone or in combination of two or more, but dichloromethane, chloroform and the like are preferably used.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  When R2 of the compound represented by (Ic) is a cyano group, the compound represented by (IVa) can be obtained by reacting a known cyanating reagent in the presence or absence of a base.

  As the cyanating reagent, bromocyanide, iodocyanide, 1-cyanoimidazole, 1-cyanobenzotriazole, substituted or unsubstituted benzenesulfonylcyanide and the like can be used.

  When the reaction is performed in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal acetates such as sodium acetate, and tertiary amines such as triethylamine. Substituted or unsubstituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane , Aliphatic hydrocarbons such as heptane and octane, halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene, and one or more solvents such as water Possible, diethyl ether, ethers such as tetrahydrofuran, dichloromethane, it is preferable to use a halogenated hydrocarbon such as chloroform.

  The reaction can usually be carried out at 0 to 100 ° C., and it is preferable to add a cyanating reagent at 0 ° C. and slowly raise the temperature to about 20 to 50 ° C.

  The compound represented by (VIa) is a compound represented by the following chemical formula (VII):

[R1 is the same as above]
In the presence or absence of an acid, H ₂ N—R 3 R 4 [R 3, R 4 has the same meaning as defined in chemical formula (I) above] is added to form an imine, followed by reduction. It can be obtained by carrying out the reaction.

  The reaction preferably uses a solvent, and the solvent is preferably a lower alcohol such as methanol or ethanol, dichloromethane, chloroform or the like, but acetonitrile or the like can also be used.

  In the case of using an acid, for example, hydrochloric acid, substituted, unsubstituted benzenesulfonic acid, acetic acid and the like can be used.

  The reduction reaction can be performed using a hydride reducing reagent such as sodium borohydride, sodium cyanoborohydride, or sodium triacetoxyborohydride.

Alternatively, the reduction reaction can also be performed by a catalytic hydrogenation reaction using a metal catalyst. As the metal catalyst, palladium, platinum, rhodium, nickel, iron or the like can be used.
The reaction temperature can usually be in the range of 20 ° C to 100 ° C.

  (6) The compound represented by the following chemical formula (Id) is

[Ar, R2, R3, R8 have the same meaning as defined in chemical formula (I) above]
The compound represented by the following chemical formula (VIII), which can be synthesized by the method described in the literature (Journal of Medicinal Chemistry 1999, 42 (12), 2227-2234), is represented by carbon disulfide, R8-X in the presence of a base. It can be obtained by reacting the compound [R8 has the same meaning as defined in the above chemical formula (I), X represents a halogen atom].

[Ar has the same meaning as defined in chemical formula (I) above]
Bases include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and copper carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, metal oxides such as copper oxide and magnesium oxide, Tertiary amines such as triethylamine and unsubstituted or substituted pyridines such as 4-dimethylaminopyridine can be used, but a strong base such as potassium t-butyrate is preferably used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, hexane , Aliphatic hydrocarbons such as heptane and octane, halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene, and one or more solvents such as water Possible, it is preferable to use ethers such as tetrahydrofuran.

  The reaction can usually be carried out at −80 to 100 ° C., but preferably carried out at 20 to 50 ° C.

  The compound represented by the chemical formula (Ie) is

[Wherein, Ar, R1, Y, and R4e are defined as above]
In the following formula, a compound represented by (IX) and a compound represented by ArCH (R1) X [Ar, R1 are as defined above, X represents halogen or OTs, OMs, etc.] It can be obtained by reacting in the presence or absence.

[Where Y and R4e are defined as above]
When the reaction is carried out in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, and triethylamine. Tertiary amines such as pyridine, pyridines having unsubstituted or substituted groups such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be carried out without solvent or using a solvent that does not affect the reaction. When a solvent is used, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, diethyl Ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol, propanol and isopropyl alcohol, ketones such as acetone and methyl ethyl ketone , One or more solvents such as aliphatic hydrocarbons such as hexane, heptane and octane, and halogen hydrocarbons such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene Can be used in conjunction, it is preferable to use such as acetonitrile.

  The reaction can usually be carried out at 0 to 200 ° C, and it is preferred to carry out the reaction at 60 to 80 ° C by adding a reagent at 20 to 40 ° C.

  The compound represented by the above chemical formula (IX) is the same as the compound represented by (IXa) in the following formula: R4e-C (= O) X, R4e-C (= O) OC (= O) R4e, R4eC (= O) OR '[X is a halogen atom or OTs, OMs, etc., R' represents a C1-C6 alkyl group, the definition of R4e is the same as described above] and the like, in the presence of a base, or It can be obtained by reacting in the absence.

[In the formula, the definition of Y is the same as above]
When the reaction is performed in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, Tertiary amines such as triethylamine and unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be performed using no solvent or a solvent that does not affect the reaction. When using a solvent, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform, chlorobenzene, Halogen hydrocarbons such as dichlorobenzene and solvents such as water can be used alone or in combination, but dimethylformamide, acetonitrile, ethers, Rorometan, it is preferable to use such as chloroform.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  The compound represented by the above reaction formula (IX) comprises a compound represented by the above (IXa) and a carboxylic acid represented by R4e-COOH [the definition of R4e- is the same as described above] And can be obtained by reacting in the presence or absence of a base.

  As the dehydrating condensing agent, carbodiimide compounds such as dicyclohexylcarbodiimide and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride can be used.

  When the reaction is carried out in the presence of a base, examples of the base include carbonates such as potassium carbonate and sodium carbonate, tertiary amines such as triethylamine, unsubstituted or substituted groups such as pyridine and 4-dimethylaminopyridine. The pyridine which has can be used.

  The reaction is preferably performed using a solvent. For example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, ethyl acetate, butyl acetate Esters such as, aromatic hydrocarbons such as benzene, xylene and toluene, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, halogens such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene Hydrocarbons can be used alone or in combination of two or more, but dichloromethane, chloroform, etc. are preferably used.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  The compound represented by the above formula (Ie) is a compound represented by the following chemical formula (IXb) or a salt thereof, R4e-C (= O) X, R4e-C (= O) OC (= O) R4e R4e-C (= O) OR '[X is a halogen atom, R' is a C1-C6 alkyl group, and R4e is as defined above], etc., in the presence of a base or non- It can also be obtained by reacting in the presence.

[Wherein, Ar, R1, and Y are defined as above]
When the reaction is performed in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, Tertiary amines such as triethylamine and unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be performed using no solvent or a solvent that does not affect the reaction. When using a solvent, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform, chlorobenzene, Halogen hydrocarbons such as dichlorobenzene and solvents such as water can be used alone or in combination, but dimethylformamide, acetonitrile, ethers, Rorometan, it is preferable to use such as chloroform.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  The compound represented by the above reaction formula (Ie) is obtained by dehydrating a compound represented by the above (IXb) or a salt thereof and a carboxylic acid represented by R4e-COOH [the definition of R4e is the same as described above]. It can also be obtained by reacting in the presence or absence of a base using a condensing agent.

  As the dehydrating condensing agent, carbodiimide compounds such as dicyclohexylcarbodiimide and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride can be used.

  When the reaction is carried out in the presence of a base, examples of the base include carbonates such as potassium carbonate and sodium carbonate, tertiary amines such as triethylamine, unsubstituted or substituted groups such as pyridine and 4-dimethylaminopyridine. The pyridine which has can be used.

  The reaction is preferably performed using a solvent. For example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, ethyl acetate, butyl acetate Esters such as, aromatic hydrocarbons such as benzene, xylene and toluene, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, halogens such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene Hydrocarbons can be used alone or in combination of two or more, but dichloromethane, chloroform, etc. are preferably used.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  The compound represented by the above (IXb) is obtained by combining a compound represented by the above (IXa) with a compound represented by ArCH (R1) X [wherein the definitions of Ar, R1, and X are the same as those described above]. It can be obtained by reacting in the presence or absence.

  When the reaction is performed in the presence of a base, examples of the base include alkali metal hydrides such as sodium hydride, carbonates such as potassium carbonate and sodium carbonate, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, Tertiary amines such as triethylamine and unsubstituted or substituted pyridines such as pyridine and 4-dimethylaminopyridine can be used.

  The reaction can be performed using no solvent or a solvent that does not affect the reaction. When using a solvent, for example, amides such as dimethylformamide and dimethylacetamide, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, ethers such as diethyl ether and tetrahydrofuran, esters such as ethyl acetate and butyl acetate, Aromatic hydrocarbons such as benzene, xylene and toluene, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as hexane, heptane and octane, dichloromethane, chloroform, chlorobenzene, Halogen hydrocarbons such as dichlorobenzene and solvents such as water can be used alone or in combination, but dimethylformamide, acetonitrile, ethers, Rorometan, it is preferable to use such as chloroform.

  The reaction can usually be carried out at −80 to 100 ° C., preferably 20 to 50 ° C.

  When synthesizing (Ie) from the compound represented by the chemical formula (IXa) via (IX) or synthesizing (Ie) from the compound represented by the chemical formula (IXa) via (IXb), ( (IX) or (IXb) can be continuously reacted without taking out, and (IXa) to (Ie) can be carried out simultaneously in the same vessel.

  Next, the present invention will be described more specifically with reference to examples, but the present invention is not limited to the examples.

Reference Example 1: 2-chloro-5- [N- (2-methylthioethyl)] aminomethylpyridine (Compound 23)
Dissolve 3.0 g (33 mmol) of 2-methylthio-ethylamine in 25 ml of anhydrous dimethylformamide and add 5.3 g (33 mmol) of 2-chloro-5-chloromethylpyridine and 1.6 g of sodium hydride (60%) (net 950 mg, 40 mmol) in this order. In addition, the mixture was stirred at 70 ° C. for 90 minutes. The reaction solution was cooled to 0 ° C., about 30 ml of water was added little by little to complete the reaction, and the mixture was extracted twice with about 50 ml of dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, concentrated, and purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1 → ethyl acetate → dichloromethane: methanol = 1: 19 → dichloromethane: methanol = 1: 10). Yield 4.6g (64% yield)

Synthesis Example 1: 2-Chloro-5- [N-cyano-N- (2-methylthioethyl)] aminomethylpyridine (Compound 1)
4 ml of anhydrous diethyl ether was added to 123 mg (1.16 mmol) of bromocyanide and cooled to 0 ° C. To this, 2-chloro-5- [N- (2-methylthioethyl)] aminomethylpyridine (Reference Example 1) (250 mg; 1.16 mmol) and sodium acetate 95 mg (1.16 mmol) dissolved in 3 ml of anhydrous diethyl ether were added in this order. In addition, the mixture was stirred overnight at room temperature. About 10 ml of 1% aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was stirred for 1 hour, and about 20 ml of diethyl ether was added for liquid separation. The diethyl ether layer was washed with about 10 ml of water and 1% hydrochloric acid. About 10 ml in that order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Yield 209 mg (75% yield).

Synthesis Example 2: 2-Chloro-5- [N-formyl-N- (2-methylthioethyl)] aminomethylpyridine (Compound 29)
To 132 mg (0.61 mmol) of 2-chloro-5- [N- (2-methylthio) ethyl] aminomethylpyridine (Reference Example 1), 10 ml of ethyl formate was added and refluxed for 3 hours. After returning the reaction solution to room temperature, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 7: 3 → 1: 1) to obtain the desired product. Yield 159 mg (81% yield).

Synthesis Example 3: 2-Chloro-5- [N-trifluoroacetyl-N-ethyl] aminomethylpyridine (Compound 21)
A solution of trifluoroacetic anhydride (140 mg; 0.67 mmol) in 5 ml of anhydrous dichloromethane was mixed with ethyl- (2-chloro-5-pyridylmethyl) amine (120 mg; 070 mmol) and triethylamine (101 mg) synthesized by the method described in US2009306041. 1 mmol) was added dropwise to a solution of 5 ml of anhydrous dichloromethane with ice cooling. After the dropwise addition and stirring at room temperature overnight, the reaction mixture was washed with ice-cooled 1% aqueous sodium hydroxide solution, water, 1% hydrochloric acid and then water in that order and dried over anhydrous magnesium sulfate. The target product was obtained by distilling off the solvent under reduced pressure. Yield 107 mg (78% yield).

Synthesis Example 4: 2-Chloro-5- (N-cyano-N-2-isopropyl) aminomethylpyridine (Compound 15)
To 50 mg (0.26 mmol) of 2-chloro-5-aminoethylpyridine, 2 ml of acetone and 1 ml of methanol were added, 43 mg (0.52 mmol) of sodium acetate was added, and the mixture was stirred at room temperature for 4 hours. Subsequently, 30 mg (0.78 mmol) of sodium borohydride was added and stirred at room temperature for 1 hour. The reaction mixture was filtered and concentrated, and ethyl acetate and water were added to separate the layers. The organic layer was dried over anhydrous magnesium sulfate, concentrated, and purified by preparative TLC plate to obtain 2-chloro-5- [N- (2-isopropylaminomethyl)] pyridine. Yield 17mg (Yield 36%)
Using 57 mg of the obtained 2-chloro-5- [N- (2-isopropylaminomethyl)] pyridine, the desired product was obtained by the method described in Synthesis Example 1. Yield 54 mg (47% yield).

Synthesis Example 5: 2-Chloro-5- [N-cyano-N- (2-propargyl)] aminomethylpyridine (Compound 42)
Dissolve 2-chloro-5-aminoethylpyridine 1.50 g (10.6 mmol) in anhydrous dimethylformamide 10 ml, add sodium hydride (60%) 486 mg (net 292 mg, 12.7 mmol) and propargyl bromide 1.25 g (10.6 mmol) in this order. The mixture was stirred at 70 ° C. for 3.5 hours. The reaction solution was returned to room temperature, water was slowly added to stop the reaction, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated, and purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give 2-chloro-5- [N- (2-propargyl)] aminomethylpyridine. Obtained. Yield 892 mg (47% yield)
Using 60 mg of the obtained 2-chloro-5- [N- (2-propargyl)] aminomethylpyridine, the desired product was obtained by the method described in Synthesis Example 1. Yield 20 mg (30% yield).

Synthesis Example 6: 2-Chloro-5- [N-cyano-N- (6-chloro-3-pyridylmethyl)] aminomethylpyridine (Compound 17)
6-Chloro-3-chloromethylpyridine (648 mg, 4 mmol), 50% ammonium cyanide aqueous solution (100 mg) and potassium carbonate (590 mg, 5 mmol) were suspended in acetonitrile (20 ml) and heated under reflux for 40 hours. Filtration while hot, the filtrate was concentrated and the residue was washed with ether and water. The viscous product was crystallized from a small amount of methanol to obtain the desired product. Yield 28mg
1H-NMR (CDCl3, δ, ppm): 4.17 (4H, s), 7.40 (2H, d), 7.68 (2H, dd), 8.31 (2H, d)
IR: 2207 (CN)
MS: m / z = 293 (M + H)

Synthesis Example 7: 4-chloro- [N-cyano-N- (4-chlorobenzyl)] aminomethylbenzene (Compound 55)
In the same manner as in Synthesis Example 6, the title compound was obtained from 1.61 g of 4-chlorobenzyl chloride. Yield 450 mg (15% yield).
1H-NMR (CDCl3, δ, ppm): 4.10 (2H, s), 7.23 (2H, d), 7.36 (2H, d)
MS: m / z = 291 (M + H)

Synthesis Example 8 N- [1- (6-chloro-3-pyridyl) ethyl] -N-cyanoethylamine (Compound 18)
6-Chloro-3-acetylpyridine (1.03 g, 0.3 mmol) and 30% ethylamine methanol solution (1.0 ml) were mixed in 8 ml of chloroform and refluxed. After 8 hours, 1 ml of 30% ethylamine methanol solution was added, and stirring was continued for 12 hours at the same temperature. Chloroform was distilled off and the residue was dissolved in 10 ml of methanol and cooled on ice. Sodium borohydride (1 g) was added little by little and stirred overnight. Methanol was distilled off and the residue was extracted with acetonitrile. The extract was concentrated under reduced pressure. Acetonitrile extraction and concentration under reduced pressure were repeated twice more, then the residue was dissolved in chloroform, washed with 1% NaOHaq, and the chloroform phase was dried with solid KOH. Chloroform was distilled off under reduced pressure to obtain 790 mg of a crude product of N- [1- (6-chloro-3-pyridyl) ethyl] -N-ethylamine (purity: 80%).
Using 100 mg of the obtained crude product of N- [1- (6-chloro-3-pyridyl) ethyl] -N-ethylamine, the target product was obtained by the method described in Synthesis Example 1. Yield 55mg (Yield 60%)
1H-NMR (CDCl3, δ, ppm): 1.25 (3H, t), 1.66 (3H, d), 2.91 (2H, m), 4.14 (1H, q), 7.37 (1H, d), 7.73 (1H, dd), 8.30 (1H, d)
IR: 2211 (CN): 2206 (CN)

Synthesis Example 9: 2- [N- (6-chloro-3-pyridylmethyl) cyanamide] ethyl methylcarbonotrithioate (Compound 6)
15 ml of (6-chloro-3-pyridylmethyl) -2-imino-1,3-thiazolidine (228 mg, 1 mmol) synthesized by the method described in the literature (Journal of Medicinal Chemistry 1999, 42 (12), 2227) Potassium t-butyrate (112 mg, 1 mmol) was added to a solution dissolved in tetrahydrofuran, and the mixture was stirred for 30 minutes at room temperature. Then, carbon disulfide (228 mg, 3 mmol) was added little by little, and stirring was further continued for 1 hour. Methyl iodide (142 mg, 1 mmol) was added dropwise and stirred for 2 hours. The insoluble solid was filtered off through celite, and the filtrate was concentrated under reduced pressure. From the viscous residue, a yellow oily target product was isolated by silica gel column chromatography using ethyl acetate / hexane (1: 1, volume ratio) as a developing solvent. Yield 130 mg (41%)
1H-NMR (CDCl3, δ, ppm): 2.76 (3H, s), 3.31 (2H, t), 3.63 (2H, t), 4.28 (2H, s), 7.38 (1H, d), 7.73 (1H, dd), 8.35 (1H, d)
IR: 2211 (CN)

Synthesis Example 10: 2-Chloro-5- [N-trifluorosulfonyl-N- (2-propynyl)] aminomethylpyridine (Compound 152)
104 mg (0.58 mmol) of 2-chloro-5- [N- (2-propynyl)] aminomethylpyridine obtained by the method described in Synthesis Example 5 was dissolved in 10 ml of anhydrous dichloromethane, and 191 μl of trifluorosulfonic anhydride (1.16 mmol, 326 mg) was added and stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was diluted with dichloromethane, washed with 1% aqueous sodium hydroxide solution and 1% aqueous hydrochloric acid solution in that order, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and silica gel column chromatography (hexane: ethyl acetate = The product was obtained after purification in 2: 8). Yield 55 mg (Yield 30%)

Synthesis Example 11: 2-Chloro-5- [N-cyano-N- (cyclopropylmethyl)] aminomethylpyridine (Compound 71)
30 mg (0.18 mmol) of N-[(6-chloropyridin-3-yl) methyl] cyanamide synthesized by the method of Comparative Example was dissolved in 3 ml of anhydrous DMF, and 10 mg of sodium hydride (60%) (net 6 mg, 0.26 mmol) And stirred at room temperature for 20 minutes. Subsequently, 52 μg (0.57 mmol) of (chloromethyl) cyclopropane and 5 mg of potassium iodide were added in this order, and the mixture was stirred at room temperature for 20 hours. After completion of the reaction, a small amount of water was added to the reaction solution to stop the reaction, and the solution was separated with 1% hydrochloric acid and ethyl acetate. The organic layer was washed with 1% hydrochloric acid, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified with a preparative TLC plate (one 0.5 mm plate, developed with hexane: ethyl acetate = 1: 1) to obtain the desired product. Got. Yield 18mg (45% yield)

Synthesis Example 12: 2- [N- (6-Chloro-3-pyridylmethyl) cyanamide] ethyl O-ethylcarbonodithioate (Compound 86)
N-[(6-chloropyridin-3-yl) methyl] cyanamide 2.00 synthesized by the method of the comparative example under ice-cooling by dissolving 8.86 g (24.0 mmol) of 1,2-bis (tosyloxy) ethane in 100 ml of anhydrous DMF g (12.0 mmol), NaH (60%) 500 mg (net 300 mg, 13.2 mmol) and KI 44 mg were added in this order, and the mixture was stirred at room temperature for 80 minutes. After completion of the reaction, methanol was added little by little at 0 ° C., followed by water to stop the reaction. Ethyl acetate and 1% hydrochloric acid are added thereto for liquid separation, and the organic layer is washed with 1% hydrochloric acid, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and silica gel column chromatography (hexane: ethyl acetate = 2: 8 → 6: 4). When the fraction containing the target product was collected and concentrated, DMF remained. A small amount of ethyl acetate was added, washed twice with 1% hydrochloric acid, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to remove DMF. 2- [N- (6-Chloro-3-pyridylmethyl) cyanamide] ethyl 4-methylbenzenesulfonate (Compound 84) was obtained. Yield 1.43 g (33% yield).

  50 mg (0.14 mmol) of 2- [N- (6-chloro-3-pyridylmethyl) cyanamide] ethyl 4-methylbenzenesulfonate synthesized by the method described above by adding 3 ml of anhydrous acetonitrile to 45 mg (0.28 mmol) of potassium ethylxanthate Was dissolved in 2 ml of acetonitrile, and the mixture was stirred at 50 ° C. for 50 minutes. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and ethyl acetate and 1% hydrochloric acid were added to separate the layers. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified with a preparative TLC plate (one 0.5 mm plate, liquid separation with hexane: ethyl acetate = 2: 3) to obtain the desired product. Yield 23 mg (18% yield).

Synthesis Example 13: 2- [N- (6-chloro-3-pyridylmethyl) cyanamide] ethyl benzyl (ethyl) carbamodithioate (Compound 85)
Benzylethylamine 55 mg (0.41 mmol) was dissolved in anhydrous THF 5 ml, potassium t-butyrate 46 mg (0.41 mmol) was added, and the mixture was stirred at room temperature for 20 minutes. Subsequently, carbon disulfide 49 μg (62 mg, 0.41 mmol), 2- [N- (6-chloro-3-pyridylmethyl) cyanamido] ethyl 4-methylbenzenesulfonate (Compound 84) 50 mg (Compound 84) synthesized by the method of Synthesis Example 12 0.14 mmol) dissolved in anhydrous THF (3 ml) and potassium iodide (5 mg) were added in this order, and the mixture was stirred at 40 ° C. for 1 hour. After completion of the reaction, the reaction was stopped by adding a small amount of water, the reaction solution was filtered using Celite, and the filtrate was concentrated. Purification by silica gel column chromatography (hexane: ethyl acetate = 7: 3) gave the desired product. Yield 41 mg (72% yield).

  Tables 6 to 9 show spectrum data of the compounds obtained in Synthesis Examples 1 to 13 and compounds obtained by the same method.

In addition, the synthesis method in a table | surface was described as follows.
A: Method similar to Synthesis Examples 1-5, B: Method similar to Synthesis Examples 6 and 7, C: Method similar to Synthesis Example 8, D: Method similar to Synthesis Example 9, E: Same as Synthesis Example 11 Method F: Method similar to Synthesis Examples 12 and 13

Synthesis Example 14 N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide (Compound 212)
(1) 25 g (270 mmol) of 2-aminopyridine was dissolved in 200 ml of anhydrous dichloromethane, and 41 ml (30 g, 300 mmol) of triethylamine was added and cooled to 0 ° C. To this, 38 ml (57 g, 270 mmol) of trifluoroacetic anhydride was added dropwise over 15 minutes, followed by stirring at room temperature for 2 hours. After completion of the reaction, the reaction solution was poured into about 100 ml of ice water and stirred for 10 minutes. The organic layer was washed twice with 150 ml of water and twice with 150 ml of 1% HCL aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 2,2,2-trifluoro. 36 g (yield 71%) of rho N- (pyridine-2 (1H) -ylidene) acetamide was obtained.
1H-NMR (CDCl3, δ, ppm): 7.20 (1H, ddd), 7.83 (1H, td), 8.20 (1H, d), 8.35 (1H, d), 10.07 (1H, brs)
13C-NMR (CDCl3, δ, ppm): 115.3, 115.5 (q), 121.6, 139.1, 147.9, 149.5, 155.3 (q)
MS: m / z = 191 (M + H)
(2) 2,2,2-trifluoro-N- (pyridine-2 (1H) -ylidene) obtained by dissolving 20 g (126 mmol) of 2-chloro-5-chloromethylpyridine in 200 ml of anhydrous acetonitrile. Acetamide 24 g (126 mmol) and potassium carbonate 21 g (151 mmol) were added, and the mixture was heated to reflux for 6 hours and then stirred at room temperature for 10 hours. After completion of the reaction, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure. Diethyl ether was added thereto for crystallization, and the resulting crystals were collected by filtration and washed well with diethyl ether and water. The obtained crystals were dried under reduced pressure at 60 ° C. for 1 hour to obtain the desired product. Yield 26 g (66% yield).
1H-NMR (CDCl3, δ, ppm): 5.57 (2H, s), 6.92 (1H, td), 7.31 (1H, d), 7.80 (1H, td), 7.87 (1H, dd), 7.99 (1H, dd), 8.48 (2H, m)
13C-NMR (CDCl3, δ, ppm): 53.8, 115.5, 117.2 (q), 122.1, 124.7, 130.0, 139.2, 140.0, 142.5, 149.7, 151.8, 158.9, 163.5 (q)
MS: m / z = 316 (M + H)
(3) Powder X-ray crystal analysis In powder X-ray diffraction, it measured on condition of the following.
Device name: RINT-2200 (Rigaku Corporation)
X-ray: Cu-Kα (40 kV, 20 mA)
Scanning range: 4 to 40 ° Sampling width: 0.02 ° Scanning speed: 1 ° / min The results are as follows (FIG. 1).
Diffraction angle (2θ) 8.7 °, 14.2 °, 17.5 °, 18.3 °, 19.8 °, 22.4 °, 30.9 °, 35.3 °
(4) Differential scanning calorimetry (DSC)
In the differential scanning calorimetry, the measurement was performed under the following conditions.
Device name: DSC-60
Sample cell: Aluminum temperature range: 50 ° C to 250 ° C (temperature increase: 10 ° C / min)
The results are shown in FIG.

  (5) Moreover, the equivalent crystal | crystallization was obtained by recrystallizing by the method (2nd-5 manufacturing method) as described in the following (i) to (iv). These crystals were subjected to powder X-ray crystal analysis and differential scanning calorimetry analysis under the same measurement conditions as described above.

(i) Second Production Method About 25 ml of hexane and about 25 ml of ethyl acetate were added to Compound 212 (700 mg), and the mixture was completely dissolved by heating to 65 ° C. in a hot water bath. This was slowly returned to room temperature and left overnight. The precipitated crystals were collected by filtration and washed with a small amount of hexane: ethyl acetate = 95: 5 solution. This was put in a desiccator and dried under reduced pressure for 2 hours to obtain 349 mg of white crystals.

The powder X-ray crystallographic analysis results are as follows (FIG. 3).
Diffraction angle (2θ) 8.5 °, 14.0 °, 17.3 °, 18.1 °, 19.6 °, 22.2 °, 30.8 °, 35.2 °
The results of differential scanning calorimetry are shown in FIG.

(ii) Third Production Method 28 ml of 2-propanol was added to Compound 212 (1.0 g) and heated to 65 ° C. in a hot water bath to completely dissolve it. This was slowly returned to room temperature and left overnight. The precipitated crystals were collected by filtration, washed with a small amount of 2-propanol, put in a desiccator and dried under reduced pressure for 2 hours to obtain 695 mg of white crystals.

  The results of differential scanning calorimetry are shown in FIG.

(iii) Fourth Production Method About 30 ml of toluene was added to Compound 212 (700 mg), and the mixture was completely dissolved by heating to 65 ° C. in a hot water bath. This was slowly returned to room temperature and left overnight. The precipitated crystals were collected by filtration, washed with a small amount of toluene, put in a desiccator and dried under reduced pressure for 2 hours to obtain 440 mg of white crystals.

The powder X-ray crystallographic analysis results are as follows (FIG. 6).
Diffraction angle (2θ) 8.6 °, 14.2 °, 17.5 °, 18.3 °, 19.7 °, 22.3 °, 30.9 °, 35.3 °
The results of differential scanning calorimetry are shown in FIG.

(iv) Fifth Production Method About 2 ml of methanol and about 2 ml of water were added to Compound 212 (50 mg), and dissolved by heating to 65 ° C. in a hot water bath. This was returned to room temperature and left overnight. The precipitated crystals were collected by filtration to obtain 16 mg of white crystals.

  The results of differential scanning calorimetry are shown in FIG.

Synthesis Example 14 Alternative method of step (1)
1.0 g (10.6 mmol) of 2-aminopyridine was dissolved in 10 ml of ethyl acetate, 1.78 ml (1.2 eq) of triethylamine was added, and 1.62 ml (1.1 eq) of trifluoroacetic anhydride was added under ice cooling. After stirring at room temperature for 2 hours, 10 ml of ethyl acetate and 10 ml of water were added, and the mixture was stirred and separated. The ethyl acetate layer was further washed twice with 10 ml of water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 1.56 g of 2,2,2-trifluoro-N- (pyridine-2 (1H) -ylidene) acetamide ( 77.2%).

Synthesis Example 14 Alternative Method 2 of Step (1)
0.94 g (10 mmol) of 2-aminopyridine was dissolved in 20 mL of THF. To this were added 2.84 g (20 mmol) of trifluoroacetic acid ethyl ester and 1.22 g (10 mmol) of dimethylaminopyridine, and the mixture was refluxed for 22 hours. After THF was distilled off, the residue was purified with a silica gel column (developing solvent: hexane / ethyl acetate 4/1), and 2,2,2-trifluoro-N- (pyridine-2 (1H) -ylidene) acetamide 0.26 g 13.7%).

Alternative Method of Synthesis Example 14 2-chloro-5-chloromethylpyridine (3.00 g, 18.6 mmol) was dissolved in anhydrous DMF (20 ml), 2-aminopyridine (1.75 g, 18.6 mmol) was added, and the mixture was added at 80 ° C for 8 hours and at room temperature for 5 hours. Stir. After completion of the reaction, DMF was distilled off under reduced pressure, and acetonitrile was added to precipitate a solid, which was collected by filtration, washed well with acetonitrile and dried to give 1-[(6-chloropyridin-3-yl) methyl] pyridine. -(1H) -imine hydrochloride (2.07 g, yield 44%) was obtained.
1H-NMR (DMSO-d6, δ, ppm): 5.65 (2H, s), 6.96 (1H, t), 7.23 (1H, m), 7.57 (1H, d), 7.80 (1H, m), 7.91 ( 1H, m), 8.28 (1H, m), 8.49 (1H, d), 9.13 (2H, brs)
50 mg (0.20 mmol) of 1-[(6-chloropyridin-3-yl) methyl] pyridine-2 (1H) -imine hydrochloride obtained by the above method was dissolved in 5 ml of anhydrous dichloromethane and 122 mg of DMAP under ice cooling. (1.00 mmol) and 50 mg (0.24 mmol) of trifluoroacetic anhydride were added in this order, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was diluted with dichloromethane, washed with 1% hydrochloric acid, and dried over anhydrous magnesium sulfate. Dichloromethane was distilled off under reduced pressure to obtain the desired product. Yield 42 mg (67% yield). NMR was consistent with that previously described.

Synthesis Example 15 2,2-Dibromo-N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -acetamide (Compound 241)
1-[(6-Chloropyridin-3-yl) methyl] pyridine-2 (1H) -imine hydrochloride 200 mg (0.78 mmol), DMAP 238 mg (1.95 mmol) obtained by the method described in Synthesis Example 14 , 224 mg (1.17 mmol) of EDC-HCl was dissolved in 10 ml of anhydrous dichloromethane, and 101 μl (202 mg, 1.17 mmol) of dibromoacetic acid was added and stirred overnight at room temperature. After completion of the reaction, the reaction mixture was diluted with dichloromethane, washed once with water and twice with 1% aqueous HCl, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain the desired product. Yield 50mg (15% yield)
1H-NMR (CDCl3, δ, ppm): 5.56 (2H, s), 5.99 (1H, s), 6.78 (1H, td), 7.33 (1H, d), 7.69 (1H, td), 7.76 (1H, dd), 7.93 (1H, dd), 8.39 (1H, d), 8.50 (1H, d)
13C-NMR (CDCl 3, δ, ppm): 44.6, 53.1, 113.7, 121.9, 124.8, 130.1, 138.2, 139.7, 141.2, 149.5, 152.0, 159.4, 172.2

Synthesis Example 16: N- [1-((6-chloro-5-fluoropyridin - 3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide (Compound 227)
4.00 g (27.6 mmol) of 2-chloro-3-fluoro-5-methylpyridine was dissolved in 80 ml of carbon tetrachloride, 7.37 g (41.4 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added, and the mixture was heated to reflux overnight. After completion of the reaction, the reaction solution was returned to room temperature, concentrated under reduced pressure, purified by silica gel column chromatography (hexane: ethyl acetate = 19: 1) and purified by 3.06 g of 5- (bromomethyl) -2-chloro-3-fluoropyridine (yield). 51%).
1H-NMR (CDCl3, δ, ppm): 4.45 (2H, s), 7.54 (1H, dd), 8.23 (1H, s)
50 mg (0.22 mmol) of 5- (bromomethyl) -2-chloro-3-fluoropyridine obtained by the above method was dissolved in 5 ml of anhydrous acetonitrile, and 2,2 obtained by the method described in Synthesis Example 14 (1) , 2-trifluoro-N- (pyridine-2 (1H) -ylidene) acetamide 42 mg (0.22 mmol) and potassium carbonate 36 mg (0.26 mmol) were added in this order, and the mixture was heated to reflux for 7 hours. After completion of the reaction, the reaction solution was returned to room temperature, insoluble matters were filtered, and the filtrate was concentrated under reduced pressure. Diethyl ether was added to this to precipitate a solid, which was collected by filtration, washed with diethyl ether and dried under reduced pressure in a desiccator to obtain the desired product. Yield 29 mg (40% yield).
1H-NMR (CDCl3, δ, ppm): 5.54 (2H, s), 6.89 (1H, td), 7.76 (1H, dd), 7.80 (1H, td), 7.85 (1H, d), 8.29 (1H, d), 8.57 (1H, d)
MS: m / z = 334 (M + H)

Synthesis Example 17 N- [1-((6-Fluoropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide (Compound 229)
2-fluoro-5-methylpyridine (500 mg, 4.50 mmol) was dissolved in carbon tetrachloride (50 ml), 1.20 g (6.76 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added, and the mixture was heated to reflux for 2.5 hours. After completion of the reaction, the reaction solution was returned to room temperature, the solvent was distilled off under reduced pressure, and purified by silica gel column chromatography (hexane: ethyl acetate = 19: 1) to give 300 mg of 5-bromomethyl-2-fluoropyridine (yield 35%). )

2,2,2-trifluoro- synthesized by the method described in Synthesis Example 14 (1) was dissolved in 57 ml (0.30 mmol) of 5-bromomethyl-2-fluoropyridine obtained by the above method in 10 ml of anhydrous acetonitrile. N- (pyridine-2 (1H) -ylidene) acetamide 57 mg (0.30 mmol) and potassium carbonate 69 mg (0.50 mmol) were added in this order, and the mixture was heated to reflux for 6 hours. After completion of the reaction, the reaction solution was returned to room temperature, insoluble matters were filtered, and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography (hexane: ethyl acetate = 1: 1 → 3: 1) gave the desired product. Yield 21 mg (23% yield).
1H-NMR (CDCl3, δ, ppm): 5.56 (2H, s), 6.89 (1H, td), 6.94 (1H, d), 7.79 (1H, td), 7.87 (1H, d), 8.03 (1H, m), 8.31 (1H, s), 8.54 (1H, d)
MS: m / z = 300 (M + H)

Synthesis Example 18: N- [1-((6-Bromopyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide (Compound 231)
2-Bromo-5-methylpyridine (500 mg, 2.92 mmol) was dissolved in carbon tetrachloride (15 ml), N-bromosuccinimide (623 mg, 3.50 mmol) and benzoyl peroxide (10 mg) were added, and the mixture was heated to reflux for 19 hours. After completion of the reaction, the reaction solution was returned to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography (hexane; ethyl acetate = 19: 1) to obtain 143 mg of 2-bromo-5-bromomethylpyridine (yield 20%). Obtained.
1H-NMR (CDCl3, δ, ppm): 4.42 (2H, s), 7.47 (1H, d), 7.59 (1H, dd), 8.38 (1H, d)
2,2,2-trifluoro- synthesized by the method described in Synthesis Example 14 (1) was prepared by dissolving 70 mg (0.28 mmol) of 2-bromo-5-bromomethylpyridine obtained by the above method in 10 ml of anhydrous acetonitrile. N- (pyridine-2 (1H) -ylidene) acetamide 54 mg (0.28 mmol) and potassium carbonate 46 mg (0.34 mmol) were added in this order, and the mixture was heated to reflux for 6 hours. After completion of the reaction, the reaction solution was returned to room temperature, insoluble matters were filtered, and the filtrate was concentrated under reduced pressure. Diethyl ether was added to this to precipitate a solid, which was collected by filtration, washed with diethyl ether and dried under reduced pressure in a desiccator to obtain the desired product. Yield 81 mg (82% yield).
1H-NMR (CDCl3, δ, ppm): 5.52 (2H, s), 6.88 (1H, t), 7.48 (1H, d), 7.78 (2H, m), 7.84 (1H, d), 8.44 (1H, d), 8.53 (1H, d)
MS: m / z = 360 (M + H)

Synthesis Example 19: 2-chloro-N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] acetamide (Compound 236)
Dissolve 70 mg (0.27 mmol) of 1-[(6-chloropyridin-3-yl) methyl] pyridine-2 (1H) -imine hydrochloride obtained by the method described in Synthesis Example 14 in 4 ml of anhydrous dichloromethane. Then, 82 mg (0.67 mmol) of DMAP, 25 mg (0.27 mmol) of chloroacetic acid and 62 mg (0.32 mmol) of EDC-HCl were added in this order, and the mixture was stirred overnight at room temperature. After completion of the reaction, dichloromethane was added to dilute, washed with water and 1% HClaq., Dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain the desired product. Yield 4 mg (5% yield).
1H-NMR (CDCl3, δ, ppm): 4.17 (2H, s), 5.46 (2H, s), 6.64 (1H, td), 7.31 (1H, d), 7.60 (1H, td), 7.64 (1H, dd), 7.80 (1H, dd), 8.32 (1H, d), 8.45 (1H, d)
MS: m / z = 296 (M + H)

Synthesis Example 20 N- [1- (1- (6-chloropyridin-3-yl) ethyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide (Compound 237)
44 mg (0.23 mmol) of 2,2,2-trifluoro-N- (pyridine-2 (1H) -ylidene) acetamide obtained by the method described in Synthesis Example 14 (1) was dissolved in 8 ml of anhydrous acetonitrile, Biosci. Biotechnol. Biochem., 67 (5), 980-988, 2003 1- (6-chloropyridin-3-yl) ethyl 4-methylbenzenesulfonate 72 mg (0.23 mmol), potassium carbonate 38 mg was added and heated to reflux for 100 minutes. After completion of the reaction, the reaction solution was returned to room temperature, insoluble matters were removed by filtration, and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography (hexane: ethyl acetate = 3: 1) gave the desired product. Yield 24 mg (Yield 32%).
1H-NMR (CDCl3, δ, ppm): 1.89 (3H, d), 6.89 (1H, td), 7.08 (1H, q), 7.32 (1H, d), 7.66 (1H, dd), 7.76 (2H, m), 8.44 (1H, d), 8.50 (1H, d)
13C-NMR (CDCl3, δ, ppm): 19.2, 55.1, 115.1, 117.4 (q), 122.0, 124, 8, 133.7, 135.2, 138.4, 141.4, 148.6, 151.9, 159.1, 163.9 (q)
MS: m / z = 330 (M + H)

Synthesis Example 21 N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide (Compound 238)
2-aminopyridine 400 mg (4.26 mmol) is dissolved in anhydrous dichloromethane 10 ml, difluoroacetic acid 322 μl (490 mg, 5.11 mmol), EDC-HCl 982 mg (5.10 mmol), DMAP 622 mg (5.11 mmol) are added, and 61 hours at room temperature. Stir. After completion of the reaction, the reaction solution was diluted with dichloromethane, washed once with water and twice with 1% HClaq. Then, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, 2,2-difluoro-N- (pyridine-2 (1H ) -Ilidene) acetamide 102 mg (14% yield) was obtained.
1H-NMR (CDCl3, δ, ppm): 6.03 (1H, t), 7.15 (1H, m), 7.78 (1H, td), 8.20 (1H, d), 8.34 (1H, dd), 8.72 (1H, brs)
100 mg (0.58 mmol) of 2,2-difluoro-N- (pyridine-2 (1H) -ylidene) acetamide obtained by the above method was dissolved in 10 ml of anhydrous acetonitrile, and 94 mg of 2-chloro-5-chloromethylpyridine ( 0.58 mmol) was dissolved in 5 ml of anhydrous acetonitrile and added, and then 84 mg (0.63 mmol) of potassium carbonate was added and heated to reflux for 140 minutes. After completion of the reaction, the reaction solution was returned to room temperature, insolubles were removed by filtration and concentrated under reduced pressure. When ether was added to this, a solid was precipitated, which was collected by filtration and dried well to obtain the desired product. Yield 63 mg (37% yield).
1H-NMR (CDCl3, δ, ppm): 5.52 (2H, s), 5.90 (1H, t), 6.79 (1H, td), 7.33 (1H, d), 7.71 (1H, m), 7.77 (1H, dd), 7.85 (1H, dd), 8.45 (1H, d), 8.50 (1H, d)
13C-NMR (DMSO-d6, δ, ppm): 53.0, 111.0 (t), 115.2, 120.7, 124.7, 131.7, 140.6, 141.6, 143.2, 150.4, 150.9, 158.3, 169.4 (t)
MS: m / z = 298 (M + H)

Synthesis Example 22 2-chloro-N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide (Compound 239)
200 mg (2.13 mmol) of 2-aminopyridine was dissolved in 5 ml of dichloromethane, 491 mg (2.55 mmol) of EDC-HCl, 311 mg (2.55 mmol) of DMAP, 187 μl of chlorodifluoroacetic acid (2.23 mmol, 290 mg) were added in this order and the mixture was stirred overnight. . After completion of the reaction, the reaction solution was diluted with dichloromethane, washed with water and 1% hydrochloric acid, dried over anhydrous magnesium sulfate, and 2-chloro-2,2-difluoro-N- (pyridine-2 (1H) -ylidene) acetamide. 105 mg (yield 24%) was obtained.
1H-NMR (CDCl3, δ, ppm): 7.19 (1H, dd), 7.82 (1H, m), 8.18 (1H, d), 8.36 (1H, d), 9.35 (1H, brs)
2-chloro-5-chloromethyl dissolved in 6 ml of anhydrous acetonitrile in 68 mg (0.33 mmol) of 2-chloro-2,2-difluoro-N- (pyridine-2 (1H) -ylidene) acetamide synthesized by the above method. Pyridine 53 mg (0.33 mmol) was added, followed by potassium carbonate 50 mg (0.36 mmol), and the mixture was heated to reflux for 1 hour. After completion of the reaction, the reaction solution was returned to room temperature and concentrated under reduced pressure. When ethyl ether was added thereto, a solid was precipitated, and was collected by filtration and dried to obtain the desired product. Yield 49 mg (45% yield).
1H-NMR (CDCl3, δ, ppm): 5.56 (2H, s), 6.92 (1H, t), 7.33 (1H, d), 7.82 (1H, m), 7.91 (1H, dd), 8.02 (1H, d), 8.45 (1H, d), 8.48 (1H, d)
13 C-NMR (CDCl 3, δ, ppm): 53.8, 115.2, 120.1 (t), 122.1, 124.8, 139.0, 140.0, 142.3, 150.0, 151.9, 159.1, 159.1, 165.8 (t)
MS: m / z = 332 (M + H)

Synthesis Example 23: 2,2,2-trichloro-N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] acetamide (Compound 235)
Dissolve 70 mg (0.27 mmol) of 1-[(6-chloropyridin-3-yl) methyl] pyridine-2 (1H) -imine hydrochloride obtained by the method described in Synthesis Example 14 in 4 ml of anhydrous dichloromethane. Then, 94 μl (0.68 mmol, 68 mg) of triethylamine and 33 μg (0.27 mmol, 49 mg) of trichloroacetyl chloride were sequentially added, followed by stirring at room temperature for 1 hour. After completion of the reaction, water was added to stop the reaction, and the mixture was separated with dichloromethane and water. The organic layer was washed once with water and twice with 1% hydrochloric acid, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. When diethyl ether was added thereto, a solid was precipitated, which was collected by filtration and dried to obtain the desired product. Yield 61 mg (62% yield).
1H-NMR (CDCl3, δ, ppm): 5.59 (2H, s), 6.86 (1H, t), 7.32 (1H, d), 7.78 (1H, td), 7.91 (2H, m), 8.43 (1H, d), 8.50 (1H, d)
MS: m / z = 364 (M + H)

Synthesis Example 24: N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,3,3,3-pentafluoropropanamide (Compound 242 )
Dissolve 2-aminopyridine 300 mg (3.19 mmol) in anhydrous dichloromethane 15 ml, add EDC-HCl 919 mg (4.78 mmol), DMAP 583 mg (4.78 mmol), pentafluoropropionic acid 397 μl (628 mg, 3.83 mmol) in this order at room temperature. Stir overnight. After completion of the reaction, the reaction solution was diluted with dichloromethane, washed once with water and twice with 1% hydrochloric acid, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 2,2,3,3,3-pentafluoro-N-. 85 mg (yield 11%) of (pyridine-2 (1H) -ylidene) propanamide was obtained.

2-Chloro-5 dissolved in 8 ml of anhydrous acetonitrile in 77 mg (0.32 mmol) of 2,2,3,3,3-pentafluoro-N- (pyridine-2 (1H) -ylidene) propanamide obtained by the above method. -52 mg (0.32 mmol) of chloromethylpyridine and 49 mg (0.35 mmol) of potassium carbonate were added, and the mixture was heated to reflux for 11 hours. After completion of the reaction, the reaction solution was returned to room temperature, insoluble matters were filtered, and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography (hexane: ethyl acetate = 1: 3) gave the desired product. Yield 12 mg (10% yield).
1H-NMR (CDCl3, δ, ppm): 5.56 (2H, s), 6.90 (1H, td), 7.32 (1H, d), 7.79 (2H, m), 7.84 (1H, d), 8.43 (1H, d), 8.56 (1H, d)
MS: m / z = 366 (M + H)

Synthesis Example 25: N- [1-((2-chloropyrimidin-5-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide (Compound 243)
1.04 g (8.13 mmol) of 2-chloro-5-methylpyrimidine was dissolved in 30 ml of carbon tetrachloride, 1.73 g (9.75 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added, and the mixture was heated to reflux for 6 hours. After completion of the reaction, the reaction solution was returned to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain 641 mg of 5-bromomethyl-2-chloropyridine (38% yield). It was.
1H-NMR (CDCl3, δ, ppm): 4.42 (2H, s), 8.66 (2H, s)
104 mg (0.50 mmol) of 5-bromomethyl-2-chloropyridine obtained by the above method was dissolved in 6 ml of anhydrous acetonitrile, and 2,2,2-trifluoro obtained by the method described in Synthesis Example 14 (1). -N- (pyridine-2 (1H) -ylidene) acetamide 96 mg (0.50 mmol) and potassium carbonate 76 mg (0.55 mmol) were added, and the mixture was heated to reflux for 1 hour. After completion of the reaction, the reaction solution was returned to room temperature, insoluble matters were removed by filtration, and the filtrate was concentrated under reduced pressure. Diethyl ether was added to this to precipitate a solid, which was collected by filtration, washed with diethyl ether, put in a desiccator and dried under reduced pressure to obtain the desired product. Yield 92 mg (58% yield).
1H-NMR (CDCl3, δ, ppm): 5.54 (2H, s), 6.98 (1H, m), 7.87 (1H, m), 8.18 (1H, m), 8.48 (1H, m), 8.83 (2H, m)
13C-NMR (CDCl3, δ, ppm): 60.0, 115.6, 117.1 (q), 122.1, 127.5, 139.2, 142.9, 158.8, 160.3 (2C), 161.4, 163.8 (q)
MS: m / z = 317 (M + H)
The spectral data of the compounds obtained by the same method as in Synthesis Examples 14 to 25 are shown in Tables 10 to 11.

Comparative Example 1: N-[(6-chloropyridin-3-yl) methyl] cyanamide (Japanese Patent Laid-Open No. 2003-26661, Compound 1))
Bromocyan 220 mg (2.09 mmol) was dissolved in anhydrous chloroform 10 ml and cooled to 0 ° C. A solution prepared by dissolving 500 mg (3.49 mmol) of 2-chloro-5-aminomethylpyridine in 10 ml of anhydrous chloroform was added dropwise thereto, and the mixture was stirred at 0 ° C. for 1 hour. The reaction solution was filtered, water was added, and the mixture was separated. The chloroform layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. This was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give 122 mg (yield 35%) of the title compound.
¹ H-NMR (CDCl ₃ , δ, ppm): 4.21 (2H, s), 5.74 (1H, brs), 7.36 (1H, d), 7.71 (1H, dd), 8.30 (1H, d)
¹³ C-NMR (CDCl ₃ , δ, ppm): 46.5, 116.1, 124.8, 131.5, 138.9, 148.9, 151.4
MS: m / z = 166 (MH)

Comparative Example 2: N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] cyanamide (Compound Document 20: Compound 20)

128 mg (0.58 mmol) of 1-[(6-chloropyridin-3-yl) methyl] pyridine-2 (1H) -imine obtained by the method described in Synthesis Example 14 was dissolved in 5 ml of anhydrous DMF, and NaH ( (Oil, purity 60%) 40 mg (net 24 mg, 1.04 mmol) was added and stirred at room temperature for 30 minutes. Bromocyan 60 mg (0.57 mmol) was added thereto and stirred overnight. After completion of the reaction, water and ethyl acetate were added to the reaction solution for liquid separation. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified with a TLC plate (one 0.5 mm plate, developed with 100% ethyl acetate) to obtain the desired product. Yield 14 mg (10% yield).
¹ N-NMR (CDCl ₃ , δ, ppm): 5.28 (2H, s), 6.55 (1H, m), 7.33 (2H, m), 7.56 (2H, m), 7.75 (1H, dd), 8.40 ( 1H, d)

Comparative Example 3: N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (2H) -ylidene] acetamide (Patent Document 4, Compound 2)

20 ml of anhydrous dichloromethane was added to 118 mg (0.46 mmol) of 1-[(6-chloropyridin-3-yl) methyl] pyridine - 2 (1H) -imine hydrochloride obtained by the method described in Synthesis Example 14 , 159 μl (1.16 mmol, 116 mg) of triethylamine and 33 μl of acetyl chloride were added and stirred at room temperature for 15 minutes. Water was added to the reaction solution to stop the reaction, and the solution was separated with chloroform and water. The organic layer was washed with a saturated aqueous solution of ammonium chloride, concentrated, and hexane was added. As a result, a solid was precipitated. The solid was collected by filtration, washed and dried well to obtain the desired product. Yield 21 mg (17% yield).
¹ N-NMR (CDCl ₃ , δ, ppm): 2.21 (3H, s), 5.35 (2H, s), 6.46 (1H, m), 7.32 (1H, d), 7.48 (2H, m), 7.75 ( 1H, d), 8.10 (1H, dd), 8.45 (1H, dd)
MS: m / z = 262 (M + H)

Comparative Example 4: 3- [1-((6-chloropyridin-3-yl) methyl) imidazolidin-2-ylidene] -1,1,1-trifluoropropan-2-one (Patent Document 5 Example 4) )

To 1.30 g (33.9 mmol, 780 mg) of NaH (oil, purity 60%) was added 15 ml of anhydrous DMF, and the mixture was cooled to 0 ° C. 1,1,1-trifluoroacetone 1.52ml (1.90g, 17.0mmol) was dripped here, and it stirred at 0 degreeC for 10 minutes. To this, 7.0 ml (110 mmol, 8.35 g) of carbon disulfide was added and stirred at 50 ° C. for 1 hour. Subsequently, the reaction solution was cooled to 0 ° C., 2.1 ml (34.0 mmol, 4.81 g) of methyl iodide was added, and the mixture was stirred overnight at room temperature. After completion of the reaction, the reaction solution was poured into ice water and stirred until the ice melted. The mixture was transferred to a separatory funnel and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 95: 5), and fractions containing the desired product were collected and concentrated under reduced pressure. When hexane was added to this, a solid was precipitated, which was collected by filtration, washed with hexane and dried well. 1,1,1-trifluoro-4,4-bis (methylthio) 3-buten-2-one 460 mg ( Yield 13%).
¹ N-NMR (CDCl ₃ , δ, ppm): 2.56 (3H, s), 2.58 (2H, s), 6.25 (1H, s)
Further, 20 ml of ethylenediamine was added to 2.0 g (12.4 mmol) of 2-chloro-5-chloromethylpyridine and stirred overnight. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, acetonitrile was added, and insoluble matters were removed by filtration. This was concentrated under reduced pressure to obtain 2.45 g (yield: 100%) of N-((6-chloropyridin-3-yl) methyl) ethane-1,2-diamine.

60 mg (0.28 mmol) of 1,1,1-trifluoro-4,4-bis (methylthio) 3-buten-2-one obtained by the above method was added to N-((6 -Chloropyridin-3-yl) methyl) ethane-1,2-diamine 77 mg (0.42 mmol) was dissolved in 8 ml of anhydrous acetonitrile and added, and the mixture was heated to reflux for 40 minutes. After completion of the reaction, the reaction solution was returned to room temperature and concentrated under reduced pressure, and ethyl acetate and water were added to separate the layers. The organic layer was washed with anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain the desired product. Yield 59 mg (69% yield).
¹ N-NMR (CDCl ₃ , δ, ppm): 3.49 (2H, t), 3.78 (2H, t), 4.40 (2H, s), 5.13 (1H, s), 7.37 (1H, d), 7.56 ( 1H, dd), 8.31 (1H, d), 9.34 (1H, brs)
m / z = 306 (M + H)

Comparative Example 5: 3- [3-((6-chloropyridin-3-yl) methyl) thiazolidine-2-ylidene] -1,1,1-trifluoropropan-2-one (Patent Document 5, Example 3)

2-aminoethane dissolved in 10 ml of ethanol in 100 mg (0.46 mmol) of 1,1,1-trifluoro - 4,4-bis (methylthio) 3-buten-2-one obtained by the method described in Comparative Example 4 After adding 36 mg (0.46 mmol) of thiol and heating to reflux for 6 hours, the mixture was stirred at room temperature for 13 hours. After completion of the reaction, ethanol was distilled off under reduced pressure, dissolved in ethyl acetate and washed once with water. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 73 mg (yield 81%) of 1,1,1-trifluoro-3- (thiazolidine-2-ylidene) propan-2-one.
¹ N-NMR (CDCl ₃ , δ, ppm): 3.35 (2H, m), 4.02 (2H, m), 5.61 (1H, s), 10.40 (1H, brs)
The obtained above manner 1,1,1-trifluoro-3- (thiazolidin-2-ylidene) propan-2-one 65 mg (0.33 mmol), 2-chloro-dissolved in anhydrous acetonitrile 8 ml - 5-chloromethyl 80 mg (0.50 mmol) of pyridine and 69 mg (0.50 mmol) of potassium carbonate were added and heated to reflux for 2 hours. After completion of the reaction, the reaction solution was returned to room temperature, insolubles were removed by filtration, and then concentrated under reduced pressure. Purification by silica gel column chromatography (hexane: ethyl acetate = 1: 1 → 1: 3) gave the desired product. Yield 53 mg (Yield 50%)
¹ N-NMR (CDCl ₃ , δ, ppm): 3.20 (2H, t), 3.73 (2H, t), 4.61 (2H, s), 5.80 (1H, s), 7.36 (1H, d), 7.53 ( 1H, dd), 8.31 (1H, d)
MS: m / z = 323 (M + H)

Comparative Example 6: 3- [1-((6-chloropyridin-3-yl) methyl) imidazolidin-2-ylidene] -1,1,1,5,5,5-hexafluoropentane-2,4- Dione (Patent Document 5 Example 5)

3- [1-((6-Chloropyridin-3-yl) methyl) imidazolidin-2-ylidene] -1,1,1-trifluoropropan-2-one obtained by the method described in Comparative Example 4 31 mg (0.10 mmol) was dissolved in 2 ml of anhydrous dichloromethane, 20 μl (0.25 mmol, 20 mg) of pyridine and 28 μl (0.20 mmol, 42 mg) of trifluoroacetic anhydride were added in this order, and the mixture was stirred at room temperature for 30 minutes. When the progress of the reaction was confirmed by TLC, the raw material remained. Therefore, 84 μl (0.60 mmol, 62 mg) of trifluoroacetic anhydride was added and stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was concentrated under reduced pressure and purified with a TLC plate (one 0.5 mm plate, developed with hexane: ethyl acetate = 2: 8) to obtain the desired product. Yield 30 mg (75% yield).
¹ N-NMR (CD ₃ OD, δ, ppm): 3.87 (4H, m), 4.51 (2H, s), 7.50 (1H, d), 7.82 (1H, dd), 8.35 (1H, d)
MS: m / z = 402 (M + H)

Comparative Example 7: N- [1-((6-chloropyridin-3-yl) methyl) imidazolidin-2-ylidene] -2,2,2-trifluoroacetamide (Patent Document 5, Example 7)

4.25 g (18.2 mmol) of dimethylcarbonimide dithioate methanesulfonate was dissolved in 30 ml of pyridine, and 3.80 ml (5.73 g, 27.3 mmol) of trifluoroacetic anhydride was added dropwise, followed by stirring overnight at room temperature. The reaction mixture was concentrated under reduced pressure and partitioned between dichloromethane and water. The organic layer was dried over anhydrous magnesium sulfate and then concentrated to obtain 5.36 g (yield 100%) of dimethyl (2,2,2-trifluoroacetyl) carbonimide dithioate.
By the method described in Comparative Example 4, 4.61 g (24.9 mmol) of N-((6-chloropyridin-3-yl) methyl) ethane - 1,2-diamine was synthesized. This was dissolved in 40 ml of anhydrous acetonitrile, 4.60 g (21.3 mmol) of dimethyl (2,2,2-trifluoroacetyl) carbonimide dithioate obtained by the above method was added, and the mixture was heated to reflux for 90 minutes. After completion of the reaction, the reaction solution was returned to room temperature and then the solvent was distilled off under reduced pressure. The precipitated solid was collected by filtration and washed with a small amount of acetonitrile to obtain the desired product. Yield 2.17 g (33% yield).
¹ N-NMR (CDCl ₃ , δ, ppm): 3.50 (2H, m), 3.76 (2H, m), 4.60 (2H, s), 7.34 (1H, d) 7.70 (1H, dd) 8.33 (1H, d)
Melting point: 168-170 ° C

Comparative Example 8: N- [3-((6-chloropyridin-3-yl) methyl) thiazolidine-2-ylidene] -2,2,2-trifluoroacetamide (Patent Document 5, Example 6)

  20 ml of ethanol was added to 77 mg (1.0 mmol) of 2-aminoethanethiol, and 216 mmol (1.0 mmol) of dimethyl (2,2,2-trifluoroacetyl) carbonimide dithioate synthesized by the method described in Comparative Example 7 was added. And stirred at room temperature overnight. After completion of the reaction, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 100 mg of 2,2,2-trifluoro-N- (thiazolidine-2-ylidene) acetamide ( Yield 51%) was obtained. This reaction was performed again by the same synthesis method, and 2,2,2-trifluoro-N- (thiazolidine-2-ylidene) acetamide was combined to obtain 350 mg.

To 2,2,2-trifluoro-N- (thiazolidine-2-ylidene) acetamide 162 mg (0.82 mmol) obtained by the above method, DMF 2 ml and THF 18 ml were added, and 2-chloro-5-chloromethylpyridine 198 mg (1.23 mmol) Then, 150 mg (1.09 mmol) of potassium carbonate was added, and the mixture was heated to reflux for 20 hours. After completion of the reaction, the reaction solution was returned to room temperature, insoluble matters were filtered, and the filtrate was concentrated under reduced pressure. This was purified with a TLC plate (two 0.5 mm plates, developed with 100% ethyl acetate) to obtain the desired product. Yield 230 mg (87% yield).
¹ N-NMR (CDCl ₃ , δ, ppm): 3.27 (2H, m), 3.73 (2H, m), 4.86 (2H, s), 7.36 (1H, d) 7.72 (1H, dd) 8.36 (1H, d)
Melting point: 96 ° C

[Formulation example]
Formulation Example 1 [Granule]
Compound 1 5% by weight
Bentonite 40% by weight
Talc 10% by weight
43% by weight clay
2% by weight calcium lignin sulfonate
The above components were pulverized and mixed uniformly, kneaded well with water, and granulated and dried to obtain granules.

Formulation Example 2 [Granule]
Compound 212 2% by weight
Sun extract P-252 5% by weight
Binder 1.5% by weight
Granulation improver 0.5% by weight
91% by weight clay
The above components were pulverized and mixed uniformly, kneaded well with water, and granulated and dried to obtain granules.

Formulation Example 3 [wettable powder]
Compound 3 30% by weight
50% by weight of clay
2% white carbon
Diatomaceous earth 13% by weight
Calcium lignin sulfonate 4% by weight
Sodium lauryl sulfate 1% by weight
The above ingredients were mixed uniformly and pulverized to obtain a wettable powder.

Formulation Example 4 [Granule wettable powder]
Compound 212 30% by weight
60% clay
Dextrin 5% by weight
Alkyl maleic acid copolymer 4% by weight
Sodium lauryl sulfate 1% by weight
The above components were uniformly pulverized and mixed, water was added and kneaded well, and then granulated and dried to obtain a granular wettable powder.

Formulation Example 5 [Flowable Agent]
Compound 8 25% by weight
POE polystyryl phenyl ether sulfate 5% by weight
Propylene glycol 6% by weight
Bentonite 1% by weight
Xanthan gum 1% aqueous solution 3% by weight
PRONAL EX-300 (Toho Chemical Co., Ltd.) 0.05% by weight
ADDAC 827 (Kay Kasei Co., Ltd.) 0.02% by weight
100% by weight of water
The total amount excluding the 1% aqueous solution of xanthan gum and an appropriate amount of water from the above mixture was premixed and then pulverized with a wet pulverizer. Thereafter, 1% aqueous solution of xanthan gum and the remaining water were added to obtain a flowable agent at 100% by weight.

Formulation Example 6 [Emulsion]
Compound 1 15% by weight
N, N-dimethylformamide 20% by weight
Solvesso 150 (ExxonMobil Co., Ltd.) 55% by weight
10% by weight of polyoxyethylene alkyl aryl ether
The above ingredients were uniformly mixed and dissolved to obtain an emulsion.

Formulation Example 7 [powder]
Compound 14 2% by weight
60% clay
Talc 37% by weight
Calcium stearate 1% by weight
The said component was mixed uniformly and the powder agent was obtained.

Formulation Example 8 [DL powder]
Compound 1 2% by weight
DL clay 94.5% by weight
2% white carbon
Calcium stearate 1% by weight
Light liquid paraffin 0.5% by weight
The said component was mixed uniformly and the powder agent was obtained.

Formulation Example 9 [Fine Granule F ]
Compound 3 2% by weight
Carrier 94% by weight
2% white carbon
Hyzol SAS-296 2% by weight
The said component was mixed uniformly and the powder agent was obtained.

Formulation Example 10 (Liquid drops)
Compound 1 10% by weight
Benzyl alcohol 74.9% by weight
15% by weight propylene carbonate
BHT 0.1 wt%
The above components were uniformly stirred and dissolved to obtain a liquefied droplet.

Formulation Example 11 [Liquid drops]
Compound 212 48% by weight
Ethanol 52% by weight
The said component was mixed uniformly and the liquid drop was obtained.

  Examples of the mixed composition of the compound of the present invention and another pesticide are described below.

Formulation Example 12 [Granule]
Compound 212 2% by weight
Probenazole
24% by weight
Binder 3.0% by weight
Granulation improver 0.5% by weight
Clay 70.5% by weight
The above components were pulverized and mixed uniformly, kneaded well with water, and granulated and dried to obtain granules.

[Test example]
<Foliage application test>
Test Example 1-1 Leafhopper disc of 5.0 cm in diameter was cut out from cabbage grown in the potter control test pot pot, and a chemical solution of the compound of the present invention having a predetermined concentration prepared so as to be 50% acetone water (added with 0.05% Tween 20) was prepared. Scattered. After air drying, the 2nd instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

  Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

As a result, compound 9,10,49,196,211,81,82,89,92,104,107,108,109,110,111,112,114,128,131,140,141,144,145,146,152,165,167,170,171,172,176,179,180,181183,184,187,237,242,240,235,241,240
Showed insecticidal activity with a death rate of 80% or more.

Test Example 1-2 A leaf disc having a diameter of 5.0 cm was cut out from cabbage grown in a potter's bait control test pot, and a chemical solution of the compound of the present invention having a predetermined concentration prepared so as to be 50% acetone water (added with 0.05% Tween 20) was prepared. Scattered. After air drying, the 2nd instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

  Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

As a result, compound 81,89,92,107,111,112,114,128,152,171,183,184,186,189,190,193,194,211,212,213,215,216,218,219,227,229,230,231,234,235,237,238,239,242,243 by 100 ppm foliar treatment
Showed insecticidal activity with a death rate of 80% or more.

Test Example 2 Cut-out leaf disc of 5.0 cm in diameter from cabbage grown in a pot- spotted carp control pot and sprayed with a chemical solution of the present compound of a predetermined concentration prepared so as to be 50% acetone water (added with 0.05% Tween 20) . After air drying, the 3rd instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

  Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, the compound 46,202,68,82,89,92,96,104,108,128,140,176,184,189,190,193,212,219,227,229,230,239 showed insecticidal activity with a mortality rate of 80% or more after treatment with 500 ppm of foliage.

Test Example 3-1 Cotton Aphid Control Test A leaf disc having a diameter of 2.0 cm was cut out from a cucumber grown in a pot, and a chemical solution of the compound of the present invention having a predetermined concentration prepared so as to be 50% acetone water (added with 0.05% Tween 20). Sprayed. After air drying, the first instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

Mortality rate (%) = {Number of dead insects / (Number of living insects tens of dead insects)} x 100

  As a result, the compound 1,2,3,6,7,8,9,10,12,14,15,18,20,21,22,25,27,29,30,31, by 500 ppm of foliage treatment 32,33,34,36,37,41,42,43,44,45,46,49,50,52,58,61,68,69,71,72,73,76,77,79,81, 82,83,85,88,89,92,96,100,101,102,103,104,119,122,131,132,135,139,165,167,170,179,182,183,184,186,189,192,193,194,196,199,200,202,208,210,211,212,219,221,222,223,225,243,80,239,234

  On the other hand, compound 1 (N-[(6-chloropyridin-3-yl) methyl] cyanamide) described in Patent Document 1 (Japanese Patent Laid-Open No. 2003-26661) was tested by the same method. The aphid death rate was 65%.

Test Example 3-2 Cotton aphid control test A leaf disc having a diameter of 2.0 cm was cut out from a cucumber grown in a pot, and 50% acetone water (added with 0.05% Tween 20) was added thereto to prepare a chemical solution of the compound of the present invention at a predetermined concentration. Sprayed. After air drying, the first instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, by treatment with 100 ppm of foliage, compounds 1,2,3,6,7,8,9,10,14,245,18,21,34,43,49,50,71,76,83,85,86, 88,89,90,91,92,93,94,96,97,102,105,113,128,131,137,138,139,140,141,145,149,152,157,163,183,186,196,199,200,204,208,212,213,214,215,216,219,222,223,225,226,238,239,232,232,236,243

Test Example 3-3 Cotton Aphid Control Test A leaf solution having a diameter of 2.0 cm was cut out from a cucumber grown in a pot, and 50% acetone water (added with 0.05% Tween 20) was added to the chemical solution of the compound of the present invention at a predetermined concentration. Sprayed. After air drying, the first instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, compound 1,2,3,6,7,8,14,18,21,82,86,88,89,90,91,94,95,128,137.138,157,199,200,212,213,214,219,226,227,229,230,231,233,234,235,236,237,238,239,240,241,242,243,244 % Insecticidal activity of more than%.

Test Example 4 Peach Aphid Control Test A leaf disc having a diameter of 2.8 cm was cut out from cabbage grown in a pot, and four adult aphids were released. One day later, the adults were removed and the number of first instar larvae laid on the leaf discs was adjusted to 10. Thereafter, a chemical solution of the compound of the present invention having a predetermined concentration prepared so as to be 50% acetone water (added with 0.05% Tween 20) was sprayed on the leaf disk infested with the hatched larvae. After air drying, the petri dish was covered and left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, the compound 1,2,3,6,7,8,9,10,11,212 showed an insecticidal activity with a mortality rate of 80% or more after 100 ppm of foliage treatment.

Test Example 5 A rice seedling grown in a pot plant control test pot plant was sprayed with a chemical solution of the compound of the present invention having a predetermined concentration prepared to be 50% acetone water (added with 0.05% Tween 20). After air drying, the 2nd instar larvae were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, the compounds 212, 213, 215, 216, 227, 229, and 230 showed an insecticidal activity with a mortality rate of 80% or more after 100 ppm of foliage treatment.

Test Example 6 Leafhopper plant control test The rice seedlings grown in pots were sprayed with a chemical solution of the compound of the present invention having a predetermined concentration prepared to be 50% acetone water (added with 0.05% Tween20). After air drying, the 2nd instar larvae were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). The insects were observed for life and death 6 days after the release, and the death rate was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, the compound 1,2,3,6,7,8 showed an insecticidal activity with a mortality rate of 80% or more after treatment with 100 ppm of foliage.

Test Example 7 A plant solution of a predetermined concentration of the compound of the present invention prepared to be 50% acetone water (added with 0.05% Tween 20) was sprayed onto a rice seedling cultivated in a white-spotted planthopper control test pot. After air drying, the 2nd instar larvae were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). Insects were observed for life and death 4 days after release, and the mortality was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, Compound 1 showed an insecticidal activity with a mortality rate of 80% or more by treatment with 100 ppm of foliage.

Test Example 8 Rice seedlings grown in a pot leafhopper control test pot were sprayed with a chemical solution of the compound of the present invention having a predetermined concentration prepared to be 50% acetone water (added with 0.05% Tween20). After air drying, the 2nd instar larvae were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). Insects were observed for life and death 4 days after release, and the mortality was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, Compound 1,212 showed an insecticidal activity with a mortality rate of 80% or more by treatment with 100 ppm of foliage.

Test Example 9 On-spot whitefly control test An adult on-spot whitefly was released in a pot-cultivated cucumber and allowed to lay eggs overnight. One day after the start of egg laying, the adults were removed and left in a thermostatic chamber (16 hours light period-8 hours dark period) at 25 ° C. Three days after the completion of egg laying, a leaf disk having a diameter of 2.0 cm was cut out from the cucumber, and after egg laying was confirmed, a chemical solution having a predetermined concentration prepared to be 50% acetone water (added with 0.05% Tween 20) was sprayed on the leaf disk. After spraying, this was left in a thermostatic chamber (16 hours light period-8 hours dark period) at 25 ° C. The insects were observed for life and death 14 days after spraying, and the death rate was calculated according to the following formula. Two continuous tests.

Mortality (%) = {(number of eggs laid−number of surviving insects) / number of eggs laid} × 100

  As a result, the compound 212,229,230 showed a high insecticidal activity with a death rate of 80% or more by treatment with 100 ppm of foliage.

  In addition, the compound 213 exhibited a high insecticidal activity with a mortality rate of 80% or more by treatment with 20 ppm of foliage.

Test Example 10-1 Triangular Thrips Control Test A leaf disk having a diameter of 2.8 cm was cut out from a green bean grown in a pot, and 50% acetone water (added with 0.05% Tween 20) was used to prepare a compound of the present invention having a predetermined concentration. The chemical solution was sprayed. After air drying, the first instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, by treatment with 500 ppm of foliage, compounds 49, 50, 85, 86, 90, 91, 93, 94, 104, 107, 108, 114, 128, 131, 135, 137, 140, 141, 144, 145, 146, 147, 152, 167, 170, 171, 172, 176, 181, 182, 183, 184, 186, 189, 190, 209, 226, 224 3,6,7,8,9,10 showed high insecticidal activity with a death rate of 80% or more.

Test Example 10-2 Citrus thrips control test A leaf disk having a diameter of 2.8 cm was cut out from a green bean grown in a pot, and 50% acetone water (added with 0.05% Tween 20) was added to this. The chemical solution was sprayed. After air drying, the first instar larvae were released. Thereafter, this was left in a constant temperature room at 25 ° C. (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. Two continuous tests.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, the compound 2,3,6,7,8,9,10,90,91,104,128,137,186,193,212,213,216,238 showed a high insecticidal activity with a mortality rate of 80% or more after treatment with 100 ppm of foliage.

Test Example 11 Akahigehosomidorikasikameka Control Test
Wheat seedling foliage 4 days after sowing was immersed for 30 seconds in a chemical solution of the compound of the present invention having a predetermined concentration prepared so as to be 50% acetone water (added with 0.05% Tween 20). After air drying, this was placed in a glass tube, and further, 2 second-instar larvae of the red bearded winged turtle were released in the same glass tube. After the release, the tube was covered and left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). In order to supply water to the wheat during the test, the wheat was sucked from below the glass tube. Three days after the treatment, the larvae were observed for survival, and the mortality was calculated according to the following formula.
Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, the compounds 132, 141, 144, 183, 184, 189, 190, 192, 193, 194, 212, 227, 229, 230, 231, 233, 236, 239, 242 and 243 exhibited insecticidal activity with a death rate of 80% or more by immersion in a chemical solution of 50 ppm.

Test Example 12 Chabanae stink bug control test Apple fruit collected in the field was sprayed with a chemical solution of the present compound of a predetermined concentration prepared to be 50% acetone water (added with 0.05% Tween 20). After air drying, this was placed in a plastic cup, and two adult Chabanae stink bugs were released. After the release, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). Six days after the release, adults were observed for life and death, and the death rate was calculated according to the following formula.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, Compound 212 showed an insecticidal activity with a mortality rate of 80% or more by treatment with 50 ppm of foliage.

Test Example 13 Rice Drosophila Control Test On the back of adults collected in the field, 1 μL (/ 1 head) of a drug solution of the compound of the present invention prepared to a predetermined concentration with acetone was locally applied with a microsyringe. After chemical treatment, adults were transferred to rice seedlings so that there were 5 per strain, and left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). After 48 hours of treatment, adult mortality was observed, and the mortality was calculated according to the following formula.

Death rate (%) = {Number of dead insects / (Number of surviving insects + Number of dead insects)} × 100

  As a result, at a treatment amount of 0.5 μg / head, compounds 1,8,212 showed a high insecticidal effect with a death rate of 80% or more.

Test Example 14 The back of an adult female reared in a housefly control test room was treated with 1 μL (one head) of a drug solution of the compound of the present invention prepared to a predetermined concentration with acetone. After the chemical treatment, adults were transferred to plastic cups so that there were 5 per cup, and left in a constant temperature room (25 hours-8 hours dark period) at 25 ° C. After 24 hours of treatment, the state of agony of adults was observed, and the rate of agony was calculated according to the following formula. The test was conducted by a two-run system.

Rate of bitter worms (%) = {number of bitter worms / (number of surviving insects + number of bitter worms)} × 100

  As a result, at a treatment amount of 2 μg / head, compounds 33, 212, 213, 214, and 216 showed a high insecticidal effect with an morbidity rate of 80% or more.

<Root immersion test>
Test Example 15 Japanese planthopper control test 48 hours after sowing, a seedling root of wheat was treated with a chemical solution of the compound of the present invention prepared to a concentration of 10% acetone water. After 72 hours of absorption of the drug from the root, 10 second larvae were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). Insects were observed for life and death 4 days after release, and the mortality was calculated according to the following formula. The test was carried out by two consecutive systems.

Mortality rate (%) = {Number of dead insects / (Number of living insects tens of dead insects)} x 100

  As a result, the compound 212,213,215,216,222,223,226,227,228,230,231,233,234,235,237,212,213,214,215,216,222,223,227,228,229,231,233,234,235,237,238,239,240,241 showed a high insecticidal activity with a death rate of 80% or more.

<Soil irrigation treatment test>
Test Example 16 Rice seedlings grown in a pot plant control test pot plant were subjected to soil irrigation treatment with a predetermined concentration of the compound of the present invention prepared to be 10% acetone water. Three days after the treatment, 10 second-instar larvae were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. The test was carried out by two consecutive systems.

Mortality rate (%) = {Number of dead insects / (Number of living insects tens of dead insects)} x 100

  As a result, Compound 212,227,229,231,233,237,238,239,242,243 showed a high insecticidal activity with a death rate of 80% or more, and Compound 212 showed a high insecticidal activity with a death rate of 95% at a treatment amount of 0.005 mg / seedling.

Test Example 17 White- seed planthopper control test Potted rice seedlings were subjected to soil irrigation treatment with a chemical solution of the compound of the present invention prepared to a concentration of 10% acetone water. Three days after the treatment, 10 white larvae second instar larvae were released. After that, it was left in a constant temperature room at 25 ° C. (16 hours light period, 18 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. The test was carried out by two consecutive systems.

Mortality rate (%) = {Number of dead insects / (Number of living insects tens of dead insects)} x 100

  As a result, the compound 212,227,229,231 showed a high insecticidal activity with a death rate of 80% or more at a treatment amount of 0.05 mg / seedling.

Test Example 18 Rice weevil control test Potted rice seedlings were subjected to soil irrigation treatment with a chemical solution prepared to be 10% acetone water. Two days after the treatment, 5 adult rice weevil were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after the release, and the death rate was calculated according to the following formula. The test was conducted by a two-run system.

Mortality rate (%) = {Number of dead insects / (Number of living insects tens of dead insects)} x 100

  As a result, Compound 212 showed a high insecticidal activity with a death rate of 80% or more at a treatment amount of 0.1 mg / seedling.

<Effects against low-sensitivity insect pests>
Test Example 19 Rice planthopper control test planted rice seedlings were subjected to soil irrigation treatment with a chemical solution of the compound of the present invention having a predetermined concentration prepared to be 10% acetone water. Three days after the treatment, 10 second-instar larvae of low drug sensitivity were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. The test was carried out by two consecutive systems.

Mortality rate (%) = {Number of dead insects / (Number of living insects tens of dead insects)} x 100

  In addition, the test pests are insects that have been raised indoors for a long period of time (susceptible strains), (I) in 2007 in Kumamoto prefecture, and (II) in 2005 in Fukuoka prefecture, and then insects that have been raised in the room. (Field collection system) was used.

  As a result, Compound 212 showed a mortality rate of 100% when treated with 0.05 mg / seedling and a mortality rate of 90% or more when treated with 0.005 mg / seedling for all strains. On the other hand, imidacloprid was found to have a death rate (susceptible strain) of 100%, (I) 40%, and (II) 60% by treating 0.05 mg / plant.

  From this result, it was shown that the compound 212 has a high insecticidal activity against the green planthopper having a low sensitivity to imidacloprid.

Test Example 20 A rice seedling grown in a pot plant control test pot was irrigated with a chemical solution of the compound of the present invention having a predetermined concentration prepared to be 10% acetone water. Three days after treatment, 10 second-instar larvae of low drug sensitivity were released. After that, it was left in a constant temperature room at 25 ° C (16 hours light period-8 hours dark period). The insects were observed for life and death 3 days after release, and the death rate was calculated according to the following formula. The test was carried out by two consecutive systems.

Mortality rate (%) = {Number of dead insects / (Number of living insects tens of dead insects)} x 100

  In addition, the test pest used the insect (susceptibility line | branch) bred in the room | chamber generation for a long time, and the insect (field collection line | system | group) bred in the room | chamber after being collected in Kumamoto Prefecture in 2006.

  As a result, Compound 212 showed a mortality rate of 100% when treated with 0.01 mg / seedling and a mortality rate of 90% or more when treated with 0.005 mg / seedling for all strains. On the other hand, imidacloprid had a death rate (susceptible line) of 100% and (field collection line) of 50% when treated with 0.01 mg / plant. In addition, fipronil was treated with 0.01 mg / seedling and the death rate (susceptible strain) was 100% and (field collection strain) was 70%.

  From these results, it was shown that Compound 212 has high insecticidal activity against imidacloprid and fipronil-hypersensitive Himetobiko.

Test Example 21 In Vitro Metabolic Test of Compound 212 and Imidacloprid Using Housefly Crude Enzyme Extract
As described in Pest Management Science (2003), 59 (3), 347-352, and Journal of Pesticide Science (2004), 29 (2), 110-116, imidacloprid undergoes oxidative metabolism, It is known to be inactivated and is considered as one of the mechanisms for acquiring resistance. The following experiment was conducted in order to confirm the effect on pests that acquired such resistance.

  10 mL of potassium phosphate buffer (pH 7.4, containing 1 mM EDTA) was added to the housefly adult (0.645 g), and the mixture was thoroughly ground by Hiscotron (Nisshin Medical Science Instrument Co., Ltd.). Thereafter, the ground product was centrifuged at 10,000 g for 15 minutes. The obtained supernatant was further centrifuged under conditions of 100,000 g for 60 minutes to obtain a precipitate. This precipitate was dissolved in 1 mL of potassium phosphate buffer and used as a crude enzyme solution. All enzyme extraction operations were performed on ice or at 4 ° C.

  Reagents were mixed in the following ratio in a 1.5 mL tube and reacted at 25 ° C. for 40 hours. After the reaction, 1 mL of acetone was added and stirred, and the resulting precipitate was removed by centrifugation at 12000 rpm for 5 minutes. The acetone in the supernatant was distilled off and injected into LC / MS for analysis.

The above crude enzyme extract: 300uL
Compound in DMSO: 5uL
Glucose 6 phosphate solution: 5uL
NADP ⁺ solution: 5uL
Glucose 6-phosphate dehydrogenase solution: 5uL
Potassium phosphate buffer (pH7.4, containing 1mM EDTA): 180uL

<Analysis conditions>
Column: Capsule pack C18MG
Mobile phase composition:
0-3 minutes: 85% water, 5% acetonitrile, 10% formic acid aqueous solution (0.1v / v%)
3-30 minutes: 85 → 25% water, 5 → 65% acetonitrile, 10% formic acid aqueous solution (0.1v / v%)
30.1-36 min: 90% acetonitrile, 10% formic acid aqueous solution (0.1v / v%)
Column temperature: 40 ° C Flow rate: 0.35mL / min Injection volume: 100uL
UV wavelength: Compound 212: 325 nm
: Imidacloprid: 300nm

  As a result, the total area% of the metabolites was O.08 for Compound No. 212, while that for Imidacloprid was 2.55, and the amount of the metabolite of Compound No. 212 was small compared to Imidacloprid. From the above results, it was shown that the compound 212 can be effectively controlled against a resistant pest that metabolically inactivates imidacloprid.

<Control effect against animal parasitic pests>
Test Example 21 A 200 mL, 10 ppm, acetone solution of 30 ppm of a mite control compound was placed in a 4 mL glass vial. This was placed on a shaker and air-dried while rotating to form a dry film of the compound on the inner wall of the vial. After the vial was dried for 24 hours or more, 10 larvae of ticklet ticks were released and capped. The vial was placed in a constant temperature room at 25 ° C., 85% humidity and all dark conditions. Life and death were observed one day after release, and the death rate was calculated according to the following formula. The test was conducted by a two-run system.

Death rate (%) = {Number of dead insects / (Number of living insects tens of dead)} × 100

  As a result, at a throughput of 200 ppm, the compounds 1,2,3,6,7,8,9,10,11,15,18,19,20,21,39,41,42,43,45,49, 50,53,58,61,72,86,88,89,91,92,93,94,96,97,101,102,105,107,108,109,111,112,114,115,119,120,130,131,132,135,137,138,165,196,199,200,204,212,213,214 showed an insecticidal rate of 80% or more.

  At a throughput of 10 ppm, compounds 1,2,3,6,7,8,9,10,18,19,42,43,58,88,91,93,94,165,196,208,212,213,214 have a high kill rate of 80% or more. Tick effect was shown.

  In a similar test, imidacloprid had a death rate of 4% at a 10 ppm throughput.

Test Example 22 Effect of controlling ticklet tick on the surface of the mouse A back surface hair of a mouse (ICR, male, 5 weeks old) was cut by about 2 cm in diameter, and a 15 mL polystyrene conical tube cut to a height of about 1.5 cm was instantly bonded. Adhesion was performed using an agent.

  20 μL of a 1000-fold diluted solution of the pest control agent prepared in the same manner as in Formulation Example 11 was dropped onto the surface of the mouse body in the adhered tube. After sufficiently drying, 10 or more larva mites were released in the tube and capped. Three days after the release, the dead and dead ticks were observed, and the death rate was calculated according to the following formula.

Blood sucking inhibition rate (%) = 100− {number of blood sucking ticks / (number of living ticks tens of dead ticks)} × 100

  As a result, the following compound 212 showed a blood absorption inhibition rate of 91%.

Test Example 23 Effect on canine filamentous worms The activity was evaluated based on the change in the motility of microfilariae of canine filamentous worms. After dissolving in RPMI1640 liquid medium so that the compound concentration was 3.13 ppm, about 20 mice were added to each of the microfilariae of canine worms and cultured at 37 ° C. Forty-eight hours after the start of the culture, the motility of the dog filamentous microfilariae was observed, and the activity was evaluated according to the following evaluation criteria.

Evaluation Criteria A: More than 2/3 insects die
B: Some effect on most insects or more than 1/3
C: No effect ~ Less than 1/3 worms died

  As a result, compounds 1, 2, 6, 7, 8, 9, and 10 exhibited a high insecticidal effect of B or higher at a treatment amount of 3.13 ppm.

  Table 12 shows a summary of the insecticidal effects of Compound Nos. 212, 227, 229, 231, 237, 238, 239, 242, and 243, which are particularly preferred compounds in the present invention.

  In addition, Table 13 shows a comparison of the effects of Compound Nos. 212, 227, 229, 231, 237, 238, 239, 242, and 243, which are particularly preferred compounds of the present invention, on the drug-insensitive insect pests.

  The amine derivative of the present invention has an excellent insecticidal effect against a large number of pests, such as diamondback moth, scallop, cotton aphid, Japanese brown planthopper, brown planthopper, leafhopper, mite, and many other pests. In addition, particularly against planthoppers, a high effect can also be shown on insect species with low drug sensitivity. Furthermore, the treatment with soil or a cultivation carrier also shows an effect, and since the opportunity for the operator to be exposed to the drug can be reduced, it can be used safely in pest control. Therefore, the present invention can greatly contribute to the field of pest control.

Claims (9)

An amine derivative represented by the following chemical formula (Ie ′) or a salt thereof.
[Wherein Ar ′ represents an optionally substituted pyridyl group, or an optionally substituted pyrimidyl group, R 1 represents a hydrogen atom or a C1-6 alkyl group, Y represents a hydrogen atom, a halogen atom, A hydroxyl group, a C1-6 alkyl group optionally substituted by a halogen atom, a C1-6 alkyloxy group optionally substituted by a halogen atom, a cyano group, a formyl group, a nitro group, and R4e is substituted by a halogen. And a C1-6 alkyl group.
However, when Ar ′ represents a 6-chloro-3-pyridyl group, R1 represents a hydrogen atom, Y represents a 5-methyl group, and R4e does not represent a trifluoromethyl group.]   The amine derivative or the salt thereof according to claim 1, wherein Y in the chemical formula (Ie ') is a hydrogen atom or a halogen atom.   The amine derivative represented by the above formula (Ie ′) is N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroaceta. N- [1-((6-chloro-5-fluoropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1- ((6-Fluoropyridin-3-yl) methyl) pyridin-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1-((6-bromopyridin-3-yl) Methyl) pyridine-2 (1H) -ylidene] -2,2,2-trifluoroacetamide, N- [1- (1- (6-chloropyridin-3-yl) ethyl) pyridine-2 (1H)- Iridene] -2,2,2-trifluoroacetamide N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide, 2-chloro-N- [1-((6- Chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2-difluoroacetamide, N- [1-((2-chloropyrimidin-5-yl) methyl) pyridine-2 ( 1H) -Ilidene] -2,2,2-trifluoroacetamide and N- [1-((6-chloropyridin-3-yl) methyl) pyridine-2 (1H) -ylidene] -2,2,3 The amine derivative or the salt thereof according to claim 1, which is a compound selected from the group consisting of 1,3,3-pentafluoropropanamide.   For at least one insect species selected from the group consisting of lepidopterous insects, semilepidopterous insects, thrips insect pests, diptera insects, coleoptera insects, animal parasitic fleas and mites, and dog filamentous insects The amine derivative or salt thereof according to any one of claims 1 to 3, which has a controlling activity.   A pest control agent comprising at least one amine derivative or salt thereof according to any one of claims 1 to 4.   A method for controlling pests in a subject other than humans using the amine derivative or salt thereof according to any one of claims 1 to 4 or the pest control agent according to claim 5.   The amine derivative according to any one of claims 1 to 4 or a salt thereof, or the pest control agent according to claim 5, wherein the nutrient solution in plant seed, root, tuber, bulb, rhizome, soil, hydroponic culture, The method according to claim 6, comprising treating the solid medium in hydroponics or a carrier for growing the plant to allow the compound to permeate into the plant.   The method according to claim 6 or 7, wherein the pest is an agricultural or horticultural pest or an animal parasitic pest.   The method according to any one of claims 6 to 8, wherein the pest is a drug-resistant pest.